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TFEB controls expression of human syncytins during cell–cell fusion Genes Dev. (IF 7.5) Pub Date : 2024-08-21 Meagan N. Esbin, Liza Dahal, Vinson B. Fan, Joey McKenna, Eric Yin, Xavier Darzacq, Robert Tjian
During human development, a temporary organ is formed, the placenta, which invades the uterine wall to support nutrient, oxygen, and waste exchange between the mother and fetus until birth. Most of the human placenta is formed by a syncytial villous structure lined by syncytialized trophoblasts, a specialized cell type that forms via cell–cell fusion of underlying progenitor cells. Genetic and functional
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The MYC–MAF–SAGA axis drives oncogenic gene expression in multiple myeloma Genes Dev. (IF 7.5) Pub Date : 2024-08-21 Hongkuan Wang, Hong Wen, Xiaobing Shi
The SAGA complex is an evolutionarily conserved histone acetyltransferase complex and transcription coactivator essential for development and disease. Dysregulation of SAGA is implicated in various human diseases, including cancer. In this issue of Genes & Development, Chen et al. (doi/10.1101/gad.351789.124) uncover a critical role for SAGA in multiple myeloma wherein SAGA's ADA2B component is required
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The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma Genes Dev. (IF 7.5) Pub Date : 2024-08-21 Ying-Jiun C. Chen, Govinal Badiger Bhaskara, Yue Lu, Kevin Lin, Sharon Y.R. Dent
Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation
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An old dog with new tricks: TFEB promotes syncytin expression and cell fusion in the human placenta Genes Dev. (IF 7.5) Pub Date : 2024-08-22 Stephen J Renaud
In the human placenta, cell fusion is crucial for forming the syncytiotrophoblast, a multinucleated giant cell essential for maintaining pregnancy and ensuring fetal health. The formation of the syncytiotrophoblast is catalyzed by the evolutionarily modern fusogens syncytin-1 and syncytin-2. In this issue of Genes & Development, Esbin and colleagues (doi:10.1101/gad.351633.124) reveal a critical role
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Therapeutic targeting of RNA for neurological and neuromuscular disease Genes Dev. (IF 7.5) Pub Date : 2024-08-14 Jodi. L. Bubenik, Marina M. Scotti, Maurice S. Swanson
Neurological and neuromuscular diseases resulting from familial, sporadic, or de novo mutations have devasting personal, familial, and societal impacts. As the initial product of DNA transcription, RNA transcripts and their associated ribonucleoprotein complexes provide attractive targets for modulation by increasing wild-type or blocking mutant allele expression, thus relieving downstream pathological
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Corrigendum: Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Mikkel Rohde, Mads Daugaard, Mette Hartvig Jensen, Kristian Helin, Jesper Nylandsted, Marja Jäättelä
Genes & Development 19: 570–582 (2005)
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Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Pei Wen, Huiyan Lei, Hua Deng, Su Deng, Carla Rodriguez Tirado, Meiling Wang, Ping Mu, Yonggang Zheng, Duojia Pan
Tumor suppressor genes play critical roles in normal tissue homeostasis, and their dysregulation underlies human diseases including cancer. Besides human genetics, model organisms such as Drosophila have been instrumental in discovering tumor suppressor pathways that were subsequently shown to be highly relevant in human cancer. Here we show that hyperplastic disc (Hyd), one of the first tumor suppressors
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A developmental mechanism to regulate alternative polyadenylation in an adult stem cell lineage Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Lorenzo Gallicchio, Neuza R. Matias, Fabián Morales-Polanco, Iliana Nava, Sarah Stern, Yi Zeng, Margaret T. Fuller
Alternative cleavage and polyadenylation (APA) often results in production of mRNA isoforms with either longer or shorter 3′ UTRs from the same genetic locus, potentially impacting mRNA translation, localization, and stability. Developmentally regulated APA can thus make major contributions to cell type-specific gene expression programs as cells differentiate. During Drosophila spermatogenesis, ∼500
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What goes up must come down: off switches for regulatory RNAs Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Katherine McJunkin, Susan Gottesman
Small RNAs base pair with and regulate mRNA translation and stability. For both bacterial small regulatory RNAs and eukaryotic microRNAs, association with partner proteins is critical for the stability and function of the regulatory RNAs. We review the mechanisms for degradation of these RNAs: displacement of the regulatory RNA from its protein partner (in bacteria) or destruction of the protein and
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Tolerance thresholds underlie responses to DNA damage during germline development Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Gloria Jansen, Daniel Gebert, Tharini Ravindra Kumar, Emily Simmons, Sarah Murphy, Felipe Karam Teixeira
Selfish DNA modules like transposable elements (TEs) are particularly active in the germline, the lineage that passes genetic information across generations. New TE insertions can disrupt genes and impair the functionality and viability of germ cells. However, we found that in P–M hybrid dysgenesis in Drosophila, a sterility syndrome triggered by the P-element DNA transposon, germ cells harbor unexpectedly
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Comparing the roles of sex chromosome-encoded protein homologs in gene regulation Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Ellen Lavorando, Michael C. Owens, Kathy Fange Liu
The X and Y chromosomes play important roles outside of human reproduction; namely, their potential contribution to human sex biases in physiology and disease. While sex biases are often thought to be an effect of hormones and environmental exposures, genes encoded on the sex chromosomes also play a role. Seventeen homologous gene pairs exist on the X and Y chromosomes whose proteins have critical
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SUMO promotes DNA repair protein collaboration to support alternative telomere lengthening in the absence of PML Genes Dev. (IF 7.5) Pub Date : 2024-07-01 Rongwei Zhao, Meng Xu, Xiaoyang Yu, Anne R. Wondisford, Rachel M. Lackner, Jayme Salsman, Graham Dellaire, David M. Chenoweth, Roderick J. O'Sullivan, Xiaolan Zhao, Huaiying Zhang
The alternative lengthening of telomeres (ALT) pathway maintains telomere length in a significant fraction of cancers that are associated with poor clinical outcomes. A better understanding of ALT mechanisms is therefore necessary for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins contributes to the formation of ALT telomere-associated PML bodies (APBs)
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Corrigendum: The evolutionary turnover of recombination hot spots contributes to speciation in mice Genes Dev. (IF 7.5) Pub Date : 2024-06-01 Fatima Smagulova, Kevin Brick, Yongmei Pu, R. Daniel Camerini-Otero, Galina V. Petukhova
Genes & Development 30: 266–280 (2016)
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Tert-expressing cells contribute to salivary gland homeostasis and tissue regeneration after radiation therapy Genes Dev. (IF 7.5) Pub Date : 2024-06-01 Li Guan, Vignesh Viswanathan, Yuyan Jiang, Sivakamasundari Vijayakumar, Hongbin Cao, Junfei Zhao, Deana Rae Crystal Colburg, Patrick Neuhöfer, Yiru Zhang, Jinglong Wang, Yu Xu, Eyiwunmi E. Laseinde, Rachel Hildebrand, Mobeen Rahman, Richard Frock, Christina Kong, Philip A. Beachy, Steven Artandi, Quynh-Thu Le
Salivary gland homeostasis and regeneration after radiotherapy depend significantly on progenitor cells. However, the lineage of submandibular gland (SMG) progenitor cells remains less defined compared with other normal organs. Here, using a mouse strain expressing regulated CreERT2 recombinase from the endogenous Tert locus, we identify a distinct telomerase-expressing (TertHigh) cell population located
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RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity Genes Dev. (IF 7.5) Pub Date : 2024-06-01 Rosa Luna, Belén Gómez-González, Andrés Aguilera
Genome integrity relies on the accuracy of DNA metabolism, but as appreciated for more than four decades, transcription enhances mutation and recombination frequencies. More recent research provided evidence for a previously unforeseen link between RNA and DNA metabolism, which is often related to the accumulation of DNA–RNA hybrids and R-loops. In addition to physiological roles, R-loops interfere
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Structural and biochemical analyses of the nuclear IκBζ protein in complex with the NF-κB p50 homodimer Genes Dev. (IF 7.5) Pub Date : 2024-06-01 Norman Zhu, W. Eric Rogers, David K. Heidary, Tom Huxford
As part of the efforts to understand nuclear IκB function in NF-κB-dependent gene expression, we report an X-ray crystal structure of the IκBζ ankyrin repeat domain in complex with the dimerization domain of the NF-κB p50 homodimer. IκBζ possesses an N-terminal α helix that conveys domain folding stability. Affinity and specificity of the complex depend on a small portion of p50 at the nuclear localization
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ChAHP2 and ChAHP control diverse retrotransposons by complementary activities Genes Dev. (IF 7.5) Pub Date : 2024-06-01 Josip Ahel, Aparna Pandey, Michaela Schwaiger, Fabio Mohn, Anja Basters, Georg Kempf, Aude Andriollo, Lucas Kaaij, Daniel Hess, Marc Bühler
Retrotransposon control in mammals is an intricate process that is effectuated by a broad network of chromatin regulatory pathways. We previously discovered ChAHP, a protein complex with repressive activity against short interspersed element (SINE) retrotransposons that is composed of the transcription factor ADNP, chromatin remodeler CHD4, and HP1 proteins. Here we identify ChAHP2, a protein complex
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Selective regulation of a defined subset of inflammatory and immunoregulatory genes by an NF-κB p50–IκBζ pathway Genes Dev. (IF 7.5) Pub Date : 2024-06-01 Allison E. Daly, George Yeh, Sofia Soltero, Stephen T. Smale
The five NF-κB family members and three nuclear IκB proteins play important biological roles, but the mechanisms by which distinct members of these protein families contribute to selective gene transcription remain poorly understood, especially at a genome-wide scale. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent and IκBζ-dependent genes in Toll-like receptor
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Epigenetic modulators provide a path to understanding disease and therapeutic opportunity Genes Dev. (IF 7.5) Pub Date : 2024-06-01 Madison A. Honer, Benjamin I. Ferman, Zach H. Gray, Elena A. Bondarenko, Johnathan R. Whetstine
The discovery of epigenetic modulators (writers, erasers, readers, and remodelers) has shed light on previously underappreciated biological mechanisms that promote diseases. With these insights, novel biomarkers and innovative combination therapies can be used to address challenging and difficult to treat disease states. This review highlights key mechanisms that epigenetic writers, erasers, readers
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Drosophila melanogaster Set8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation Genes Dev. (IF 7.5) Pub Date : 2024-05-01 Aaron T. Crain, Megan B. Butler, Christina A. Hill, Mai Huynh, Robert K. McGinty, Robert J. Duronio
Monomethylation of lysine 20 of histone H4 (H4K20me1) is catalyzed by Set8 and thought to play important roles in many aspects of genome function that are mediated by H4K20me binding proteins. We interrogated this model in a developing animal by comparing in parallel the transcriptomes of Set8null, H4K20R/A, and l(3)mbt mutant Drosophila melanogaster. We found that the gene expression profiles of H4K20A
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Genome organization regulates nuclear pore complex formation and promotes differentiation during Drosophila oogenesis Genes Dev. (IF 7.5) Pub Date : 2024-05-01 Noor M. Kotb, Gulay Ulukaya, Ankita Chavan, Son C. Nguyen, Lydia Proskauer, Eric F. Joyce, Dan Hasson, Madhav Jagannathan, Prashanth Rangan
Genome organization can regulate gene expression and promote cell fate transitions. The differentiation of germline stem cells (GSCs) to oocytes in Drosophila involves changes in genome organization mediated by heterochromatin and the nuclear pore complex (NPC). Heterochromatin represses germ cell genes during differentiation, and NPCs anchor these silenced genes to the nuclear periphery, maintaining
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A nuclear architecture screen in Drosophila identifies Stonewall as a link between chromatin position at the nuclear periphery and germline stem cell fate Genes Dev. (IF 7.5) Pub Date : 2024-05-01 Ankita Chavan, Randi Isenhart, Son C. Nguyen, Noor M. Kotb, Jailynn Harke, Anna Sintsova, Gulay Ulukaya, Federico Uliana, Caroline Ashiono, Ulrike Kutay, Gianluca Pegoraro, Prashanth Rangan, Eric F. Joyce, Madhav Jagannathan
The association of genomic loci to the nuclear periphery is proposed to facilitate cell type-specific gene repression and influence cell fate decisions. However, the interplay between gene position and expression remains incompletely understood, in part because the proteins that position genomic loci at the nuclear periphery remain unidentified. Here, we used an Oligopaint-based HiDRO screen targeting
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Beyond histones: the elusive substrates of chromatin regulators Genes Dev. (IF 7.5) Pub Date : 2024-05-01 Mattias Mannervik
Gene transcription is intimately linked to chromatin state and histone modifications. However, the enzymes mediating these post-translational modifications have many additional, nonhistone substrates, making it difficult to ascribe the most relevant modification. In this issue of Genes & Development, Crain and colleagues (doi:10.1101/gad.351698.124) have combined a powerful histone replacement system
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Diverse Fgfr1 signaling pathways and endocytic trafficking regulate mesoderm development Genes Dev. (IF 7.5) Pub Date : 2024-05-01 James F. Clark, Philippe Soriano
The fibroblast growth factor (FGF) pathway is a conserved signaling pathway required for embryonic development. Activated FGF receptor 1 (FGFR1) drives multiple intracellular signaling cascade pathways, including ERK/MAPK and PI3K/AKT, collectively termed canonical signaling. However, unlike Fgfr1-null embryos, embryos containing hypomorphic mutations in Fgfr1 lacking the ability to activate canonical
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Nuclear receptor signaling via NHR-49/MDT-15 regulates stress resilience and proteostasis in response to reproductive and metabolic cues Genes Dev. (IF 7.5) Pub Date : 2024-05-01 Ambre J. Sala, Rogan A. Grant, Ghania Imran, Claire Morton, Renee M. Brielmann, Szymon Gorgoń, Jennifer Watts, Laura C. Bott, Richard I. Morimoto
The ability to sense and respond to proteotoxic insults declines with age, leaving cells vulnerable to chronic and acute stressors. Reproductive cues modulate this decline in cellular proteostasis to influence organismal stress resilience in Caenorhabditis elegans. We previously uncovered a pathway that links the integrity of developing embryos to somatic health in reproductive adults. Here, we show
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Glioblastoma microenvironment—from biology to therapy Genes Dev. (IF 7.5) Pub Date : 2024-05-01 Renee D. Read, Zoe M. Tapp, Prajwal Rajappa, Dolores Hambardzumyan
Glioblastoma (GBM) is the most aggressive primary brain cancer. These tumors exhibit high intertumoral and intratumoral heterogeneity in neoplastic and nonneoplastic compartments, low lymphocyte infiltration, and high abundance of myeloid subsets that together create a highly protumorigenic immunosuppressive microenvironment. Moreover, heterogeneous GBM cells infiltrate adjacent brain tissue, remodeling
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Corrigendum: miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma Genes Dev. (IF 7.5) Pub Date : 2024-04-01 Fotini M. Kouri, Lisa A. Hurley, Weston L. Daniel, Emily S. Day, Youjia Hua, Liangliang Hao, Chian-Yu Peng, Timothy J. Merkel, Markus A. Queisser, Carissa Ritner, Hailei Zhang, C. David James, Jacob I. Sznajder, Lynda Chin, David A. Giljohann, John A. Kessler, Marcus E. Peter, Chad A. Mirkin, Alexander H. Stegh
Genes & Development 29: 732–745 (2015)
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Corrigendum: Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination Genes Dev. (IF 7.5) Pub Date : 2024-04-01 Justin B. Steinfeld, Ondrej Beláň, Youngho Kwon, Tsuyoshi Terakawa, Amr Al-Zain, Michael J. Smith, J. Brooks Crickard, Zhi Qi, Weixing Zhao, Rodney Rothstein, Lorraine S. Symington, Patrick Sung, Simon J. Boulton, Eric C. Greene
Genes & Development 33: 1191–1207 (2019)
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H2A.Z chaperones converge on E2F target genes for melanoma cell proliferation Genes Dev. (IF 7.5) Pub Date : 2024-04-01 Sina Jostes, Chiara Vardabasso, Joanna Dong, Saul Carcamo, Rajendra Singh, Robert Phelps, Austin Meadows, Elena Grossi, Dan Hasson, Emily Bernstein
High levels of H2A.Z promote melanoma cell proliferation and correlate with poor prognosis. However, the role of the two distinct H2A.Z histone chaperone complexes SRCAP and P400–TIP60 in melanoma remains unclear. Here, we show that individual subunit depletion of SRCAP, P400, and VPS72 (YL1) results in not only the loss of H2A.Z deposition into chromatin but also a reduction of H4 acetylation in melanoma
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Intron lariat spliceosomes convert lariats to true circles: implications for intron transposition Genes Dev. (IF 7.5) Pub Date : 2024-04-01 Manuel Ares, Jr., Haller Igel, Sol Katzman, John P. Donohue
Rare, full-length circular intron RNAs distinct from lariats have been reported in several species, but their biogenesis is not understood. We envisioned and tested a hypothesis for their formation using Saccharomyces cerevisiae, documenting full-length and novel processed circular RNAs from multiple introns. Evidence implicates a previously undescribed catalytic activity of the intron lariat spliceosome
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Oct4 redox sensitivity potentiates reprogramming and differentiation Genes Dev. (IF 7.5) Pub Date : 2024-04-01 Zuolian Shen, Yifan Wu, Asit Manna, Chongil Yi, Bradley R. Cairns, Kimberley J. Evason, Mahesh B. Chandrasekharan, Dean Tantin
The transcription factor Oct4/Pou5f1 is a component of the regulatory circuitry governing pluripotency and is widely used to induce pluripotency from somatic cells. Here we used domain swapping and mutagenesis to study Oct4's reprogramming ability, identifying a redox-sensitive DNA binding domain, cysteine residue (Cys48), as a key determinant of reprogramming and differentiation. Oct4 Cys48 sensitizes
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The lncRNA Malat1 is trafficked to the cytoplasm as a localized mRNA encoding a small peptide in neurons Genes Dev. (IF 7.5) Pub Date : 2024-04-01 Wen Xiao, Reem Halabi, Chia-Ho Lin, Mohammad Nazim, Kyu-Hyeon Yeom, Douglas L. Black
Synaptic function in neurons is modulated by local translation of mRNAs that are transported to distal portions of axons and dendrites. The metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is broadly expressed across cell types, almost exclusively as a nuclear long noncoding RNA. We found that in differentiating neurons, a portion of Malat1 RNA redistributes to the cytoplasm. Depletion
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An unexpected path for Malat1 in neurons: trafficking out of the nucleus for translation Genes Dev. (IF 7.5) Pub Date : 2024-04-01 Bradley W. Wright, Jeremy E. Wilusz
The Malat1 (metastasis-associated lung adenocarcinoma transcript 1) long noncoding RNA is highly and broadly expressed in mammalian tissues, accumulating in the nucleus where it modulates expression and pre-mRNA processing of many protein-coding genes. In this issue of Genes & Development, Xiao and colleagues (doi:10.1101/gad.351557.124) report that a significant fraction of Malat1 transcripts in cultured
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Corrigendium: Effects of RAS on the genesis of embryonal rhabdomyosarcoma Genes Dev. (IF 7.5) Pub Date : 2024-03-01 David M. Langenau, Matthew D. Keefe, Narie Y. Storer, Jeffrey R. Guyon, Jeffery L. Kutok, Xiuning Le, Wolfram Goessling, Donna S. Neuberg, Louis M. Kunkel, Leonard I. Zon
Genes & Development 21: 1382–1395 (2007)
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A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies Genes Dev. (IF 7.5) Pub Date : 2024-03-01 Brian Freie, Patrick A. Carroll, Barbara J. Varnum-Finney, Erin L. Ramsey, Vijay Ramani, Irwin Bernstein, Robert N. Eisenman
Oncogenic activation of MYC in cancers predominantly involves increased transcription rather than coding region mutations. However, MYC-dependent lymphomas frequently acquire point mutations in the MYC phosphodegron, including at threonine 58 (T58), where phosphorylation permits binding via the FBW7 ubiquitin ligase triggering MYC degradation. To understand how T58 phosphorylation functions in normal
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Haploinsufficiency of phosphodiesterase 10A activates PI3K/AKT signaling independent of PTEN to induce an aggressive glioma phenotype Genes Dev. (IF 7.5) Pub Date : 2024-03-01 Nicholas Nuechterlein, Allison Shelbourn, Frank Szulzewsky, Sonali Arora, Michelle Casad, Siobhan Pattwell, Leyre Merino-Galan, Erik Sulman, Sumaita Arowa, Neriah Alvinez, Miyeon Jung, Desmond Brown, Kayen Tang, Sadhana Jackson, Stefan Stoica, Prashant Chittaboina, Yeshavanth K. Banasavadi-Siddegowda, Hans-Georg Wirsching, Nephi Stella, Linda Shapiro, Patrick Paddison, Anoop P. Patel, Mark R. Gilbert
Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an independent poor prognostic marker in multiple data sets. We then combined CRISPR–Cas9 data, human spatial transcriptomic data, and human and mouse RNA
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Protein domains of low sequence complexity—dark matter of the proteome Genes Dev. (IF 7.5) Pub Date : 2024-03-01 Steven L. McKnight
This perspective begins with a speculative consideration of the properties of the earliest proteins to appear during evolution. What did these primitive proteins look like, and how were they of benefit to early forms of life? I proceed to hypothesize that primitive proteins have been preserved through evolution and now serve diverse functions important to the dynamics of cell morphology and biological
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WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases Genes Dev. (IF 7.5) Pub Date : 2024-03-01 Jung-Hoon Yoon, Karthi Sellamuthu, Louise Prakash, Satya Prakash
Purified translesion synthesis (TLS) DNA polymerases (Pols) replicate through DNA lesions with a low fidelity; however, TLS operates in a predominantly error-free manner in normal human cells. To explain this incongruity, here we determine whether Y family Pols, which play an eminent role in replication through a diversity of DNA lesions, are incorporated into a multiprotein ensemble and whether the
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NFATC2IP is a mediator of SUMO-dependent genome integrity Genes Dev. (IF 7.5) Pub Date : 2024-03-01 Tiffany Cho, Lisa Hoeg, Dheva Setiaputra, Daniel Durocher
The post-translational modification of proteins by SUMO is crucial for cellular viability and mammalian development in part due to the contribution of SUMOylation to genome duplication and repair. To investigate the mechanisms underpinning the essential function of SUMO, we undertook a genome-scale CRISPR/Cas9 screen probing the response to SUMOylation inhibition. This effort identified 130 genes whose
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Pan-cellular organelles and suborganelles—from common functions to cellular diversity? Genes Dev. (IF 7.5) Pub Date : 2024-02-01 Rico Schieweck, Magdalena Götz
Cell diversification is at the base of increasing multicellular organism complexity in phylogeny achieved during ontogeny. However, there are also functions common to all cells, such as cell division, cell migration, translation, endocytosis, exocytosis, etc. Here we revisit the organelles involved in such common functions, reviewing recent evidence of unexpected differences of proteins at these organelles
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A serine metabolic enzyme is flexing its muscle to help repair skeletal muscle Genes Dev. (IF 7.5) Pub Date : 2024-02-01 Benjámin R. Baráth, Laszlo Nagy
Metabolic reprogramming of stem cells is a targetable pathway to control regeneration. Activation of stem cells results in down-regulation of oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) and turns on glycolysis to provide fuel for proliferation and specific signaling events. How cell type-specific events are regulated is unknown. In this issue of Genes & Development Ciuffoli and
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ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice Genes Dev. (IF 7.5) Pub Date : 2024-02-01 Wen Wang, Rui Gao, Dongxu Yang, Mingli Ma, Ruge Zang, Xiangxiu Wang, Chuan Chen, Xiaochen Kou, Yanhong Zhao, Jiayu Chen, Xuelian Liu, Jiaxu Lu, Ben Xu, Juntao Liu, Yanxin Huang, Chaoqun Chen, Hong Wang, Shaorong Gao, Yong Zhang, Yawei Gao
CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation
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Coordination of histone chaperones for parental histone segregation and epigenetic inheritance Genes Dev. (IF 7.5) Pub Date : 2024-02-01 Yimeng Fang, Xu Hua, Chun-Min Shan, Takenori Toda, Feng Qiao, Zhiguo Zhang, Songtao Jia
Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3–H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3–H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using
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A maternal-effect Padi6 variant causes nuclear and cytoplasmic abnormalities in oocytes, as well as failure of epigenetic reprogramming and zygotic genome activation in embryos Genes Dev. (IF 7.5) Pub Date : 2024-02-01 Carlo Giaccari, Francesco Cecere, Lucia Argenziano, Angela Pagano, Antonio Galvao, Dario Acampora, Gianna Rossi, Bruno Hay Mele, Basilia Acurzio, Scott Coonrod, Maria Vittoria Cubellis, Flavia Cerrato, Simon Andrews, Sandra Cecconi, Gavin Kelsey, Andrea Riccio
Maternal inactivation of genes encoding components of the subcortical maternal complex (SCMC) and its associated member, PADI6, generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multilocus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly
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Psat1-generated α-ketoglutarate and glutamine promote muscle stem cell activation and regeneration Genes Dev. (IF 7.5) Pub Date : 2024-02-01 Veronica Ciuffoli, Xuesong Feng, Kan Jiang, Natalia Acevedo-Luna, Kyung Dae Ko, A. Hong Jun Wang, Giulia Riparini, Mamduh Khateb, Brian Glancy, Stefania Dell'Orso, Vittorio Sartorelli
By satisfying bioenergetic demands, generating biomass, and providing metabolites serving as cofactors for chromatin modifiers, metabolism regulates adult stem cell biology. Here, we report that a branch of glycolysis, the serine biosynthesis pathway (SBP), is activated in regenerating muscle stem cells (MuSCs). Gene inactivation and metabolomics revealed that Psat1, one of the three SBP enzymes, controls
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ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline Genes Dev. (IF 7.5) Pub Date : 2024-02-01 Kris G. Alavattam, Jasmine M. Esparza, Mengwen Hu, Ryuki Shimada, Anna R. Kohrs, Hironori Abe, Yasuhisa Munakata, Kai Otsuka, Saori Yoshimura, Yuka Kitamura, Yu-Han Yeh, Yueh-Chiang Hu, Jihye Kim, Paul R. Andreassen, Kei-ichiro Ishiguro, Satoshi H. Namekawa
H3K9 trimethylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that
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Spore germination: Two ion channels are better than one Genes Dev. (IF 7.5) Pub Date : 2024-01-01 Patrick Eichenberger
Germination is the process by which spores emerge from dormancy. Although spores can remain dormant for decades, the study of germination is an active field of research. In this issue of Genes & Development, Gao and colleagues (pp. 31–45) address a perplexing question: How can a dormant spore initiate germination in response to environmental cues? Three distinct complexes are involved: GerA, a germinant-gated
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DNA damage remodels the MITF interactome to increase melanoma genomic instability Genes Dev. (IF 7.5) Pub Date : 2024-01-01 Romuald Binet, Jean-Philippe Lambert, Marketa Tomkova, Samuel Tischfield, Arianna Baggiolini, Sarah Picaud, Sovan Sarkar, Pakavarin Louphrasitthiphol, Diogo Dias, Suzanne Carreira, Timothy C. Humphrey, Panagis Fillipakopoulos, Richard White, Colin R. Goding
Since genome instability can drive cancer initiation and progression, cells have evolved highly effective and ubiquitous DNA damage response (DDR) programs. However, some cells (for example, in skin) are normally exposed to high levels of DNA-damaging agents. Whether such high-risk cells possess lineage-specific mechanisms that tailor DNA repair to the tissue remains largely unknown. Using melanoma
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Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma Genes Dev. (IF 7.5) Pub Date : 2024-01-01 Lucas D. Caeiro, Yuichiro Nakata, Rodrigo L. Borges, Mengsheng Zha, Liliana Garcia-Martinez, Carolina P. Bañuelos, Stephanie Stransky, Tong Liu, Ho Lam Chan, John Brabson, Diana Domínguez, Yusheng Zhang, Peter W. Lewis, Salvador Aznar Benitah, Luisa Cimmino, Daniel Bilbao, Simone Sidoli, Zheng Wang, Ramiro E. Verdun, Lluis Morey
Approximately 20% of head and neck squamous cell carcinomas (HNSCCs) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided
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SpoVAF and FigP assemble into oligomeric ion channels that enhance spore germination Genes Dev. (IF 7.5) Pub Date : 2024-01-01 Yongqiang Gao, Jeremy D. Amon, Anna P. Brogan, Lior Artzi, Fernando H. Ramírez-Guadiana, Joshua C. Cofsky, Andrew C. Kruse, David Z. Rudner
Bacterial spores can remain dormant for decades yet rapidly germinate and resume growth in response to nutrients. GerA family receptors that sense and respond to these signals have recently been shown to oligomerize into nutrient-gated ion channels. Ion release initiates exit from dormancy. Here, we report that a distinct ion channel, composed of SpoVAF (5AF) and its newly discovered partner protein
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Regularly spaced tyrosines in EBF1 mediate BRG1 recruitment and formation of nuclear subdiffractive clusters Genes Dev. (IF 7.5) Pub Date : 2024-01-01 Nikolay Zolotarev, Yuanting Wang, Manyu Du, Marc Bayer, Anna Grosschedl, Ibrahim Cisse, Rudolf Grosschedl
B lineage priming by pioneer transcription factor EBF1 requires the function of an intrinsically disordered region (IDR). Here, we examine the role of regularly spaced tyrosines in the IDR as potential determinants of IDR function and activity of EBF1. We found that four Y > A mutations in EBF1 reduced the formation of condensates in vitro and subdiffractive clusters in vivo. Notably, Y > A mutant
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A mutation in the low-complexity domain of splicing factor hnRNPA1 linked to amyotrophic lateral sclerosis disrupts distinct neuronal RNA splicing networks Genes Dev. (IF 7.5) Pub Date : 2024-01-01 Yeon J. Lee, Donald C. Rio
Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease characterized by loss of motor neurons. Human genetic studies have linked mutations in RNA-binding proteins as causative for this disease. The hnRNPA1 protein, a known pre-mRNA splicing factor, is mutated in some ALS patients. Here, two human cell models were generated to investigate how a mutation in the C-terminal low-complexity
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Reviewers, Volume 37 (2023) Genes Dev. (IF 7.5) Pub Date : 2023-11-01
The editors would like to thank the Editorial Board and the following scientists who reviewed papers and provided advice during 2023.
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A nonneural miRNA cluster mediates hearing via repression of two neural targets Genes Dev. (IF 7.5) Pub Date : 2023-11-01 Binglong Zhang, Hong Duan, Joshua Kavaler, Lu Wei, Daniel F. Eberl, Eric C. Lai
We show here that mir-279/996 are absolutely essential for development and function of Johnston's organ (JO), the primary proprioceptive and auditory organ in Drosophila. Their deletion results in highly aberrant cell fate determination, including loss of scolopale cells and ectopic neurons, and mutants are electrophysiologically deaf. In vivo activity sensors and mosaic analyses indicate that these
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The steroid hormone ADIOL promotes learning by reducing neural kynurenic acid levels Genes Dev. (IF 7.5) Pub Date : 2023-11-01 George A. Lemieux, Shinja Yoo, Lin Lin, Mihir Vohra, Kaveh Ashrafi
Reductions in brain kynurenic acid levels, a neuroinhibitory metabolite, improve cognitive function in diverse organisms. Thus, modulation of kynurenic acid levels is thought to have therapeutic potential in a range of brain disorders. Here we report that the steroid 5-androstene 3β, 17β-diol (ADIOL) reduces kynurenic acid levels and promotes associative learning in Caenorhabditis elegans. We identify
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AI-assisted proofreading of RNA splicing Genes Dev. (IF 7.5) Pub Date : 2023-11-01 Ángel Guerra-Moreno, Juan Valcárcel
RNA helicases orchestrate proofreading mechanisms that facilitate accurate intron removal from pre-mRNAs. How these activities are recruited to spliceosome/pre-mRNA complexes remains poorly understood. In this issue of Genes & Development, Zhang and colleagues (pp. 968–983) combine biochemical experiments with AI-based structure prediction methods to generate a model for the interaction between SF3B1
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LINE-1 retrotransposition and its deregulation in cancers: implications for therapeutic opportunities Genes Dev. (IF 7.5) Pub Date : 2023-11-01 Carlos Mendez-Dorantes, Kathleen H. Burns
Long interspersed element 1 (LINE-1) is the only protein-coding transposon that is active in humans. LINE-1 propagates in the genome using RNA intermediates via retrotransposition. This activity has resulted in LINE-1 sequences occupying approximately one-fifth of our genome. Although most copies of LINE-1 are immobile, ∼100 copies are retrotransposition-competent. Retrotransposition is normally limited
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Restrictor synergizes with Symplekin and PNUTS to terminate extragenic transcription Genes Dev. (IF 7.5) Pub Date : 2023-11-01 Marta Russo, Viviana Piccolo, Danilo Polizzese, Elena Prosperini, Carolina Borriero, Sara Polletti, Fabio Bedin, Mattia Marenda, Davide Michieletto, Gaurav Madappa Mandana, Simona Rodighiero, Alessandro Cuomo, Gioacchino Natoli
Transcription termination pathways mitigate the detrimental consequences of unscheduled promiscuous initiation occurring at hundreds of thousands of genomic cis-regulatory elements. The Restrictor complex, composed of the Pol II-interacting protein WDR82 and the RNA-binding protein ZC3H4, suppresses processive transcription at thousands of extragenic sites in mammalian genomes. Restrictor-driven termination
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Molecular basis for PHF7-mediated ubiquitination of histone H3 Genes Dev. (IF 7.5) Pub Date : 2023-11-01 Hyun Sik Lee, Injin Bang, Junghyun You, Tae-Kyeong Jeong, Chang Rok Kim, Minsang Hwang, Jong-Seo Kim, Sung Hee Baek, Ji-Joon Song, Hee-Jung Choi
The RING-type E3 ligase has been known for over two decades, yet its diverse modes of action are still the subject of active research. Plant homeodomain (PHD) finger protein 7 (PHF7) is a RING-type E3 ubiquitin ligase responsible for histone ubiquitination. PHF7 comprises three zinc finger domains: an extended PHD (ePHD), a RING domain, and a PHD. While the function of the RING domain is largely understood
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Characterization of the SF3B1–SUGP1 interface reveals how numerous cancer mutations cause mRNA missplicing Genes Dev. (IF 7.5) Pub Date : 2023-11-01 Jian Zhang, Jindou Xie, Ji Huang, Xiangyang Liu, Ruihong Xu, Jonas Tholen, Wojciech P. Galej, Liang Tong, James L. Manley, Zhaoqi Liu
The spliceosomal gene SF3B1 is frequently mutated in cancer. While it is known that SF3B1 hotspot mutations lead to loss of splicing factor SUGP1 from spliceosomes, the cancer-relevant SF3B1–SUGP1 interaction has not been characterized. To address this issue, we show by structural modeling that two regions flanking the SUGP1 G-patch make numerous contacts with the region of SF3B1 harboring hotspot