Jacobsen, Steven E. - University of California, Los Angeles

个人简介

Steve Jacobsen did his PhD at the University of Minnesota and postdoctoral studies at the California Institute of Technology with Elliot Meyerowitz. He joined the department of Molecular Cell and Developmental Biology in 1998. He has recieved two young investigator awards for his research, from the Searle Scholars and Beckman Young Investigator Programs, and was named an HHMI Investigator in 2005.

研究领域

Cytosine DNA methylation is an epigenetic modification of DNA that is usually associated with the stable and heritable repression of gene transcription. Many methylated sequences found in genomes are transposable elements, indicating the likely ancestral role of DNA methylation in genome defense. DNA methylation is also important in imprinting, X chromosome inactivation, and the epigenetic regulation of genes. While DNA methylation is widespread in plants, fungi and animals, it has been curiously lost in some well-studied model organisms including S. cerevisiae, S. pombe, C. elegans and Drosophila. We study DNA methylation in the model plant Arabidopsis thaliana because of its facile genetics, small size, and trim genome. Furthermore, unlike other organisms like mouse, where DNA methylation mutants are inviable, Arabidopsis can tolerate mutations that virtually eliminate methylation, allowing for further study. Arabidopsis methylation mutants display developmental abnormalities because of defects in the methylation of several key genes that regulate development. We have taken advantage of the stable methylation present several of these developmental genes (epigenetic alleles), in order to perform genetic screens for mutants affecting DNA methylation. Our studies have revealed that DNA methylation is controlled by 1) the specificity of several different DNA methyltransferases, 2) targeting by other chromatin modifications such as the methylation of histone tails, and 3) targeting of specific DNA sequences by small interfering RNAs (siRNAs) and long non-coding RNAs. These screens have also uncovered novel pathways by which DNA methylated sequences are read and silenced. In addition to genetics, we rely heavily on computational biology and biochemistry in our work. We also have a small mammalian program, focused on studies of conserved regulators of DNA methylation.

近期论文

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Israel Ausin, Suhua Feng, Chaowei Yu, Wanlu Liu, Hsuan Yu Kuo, Elise L. Jacobsen, Jixian Zhai, Javier Gallego-Bartolome, Lin Wang, Ulrika Egertsdotter, Nathaniel R. Street, Steven E. Jacobsen, and Haifeng Wang. (2016) DNA methylome of the 20-gigabase Norway spruce genome. Proc. Nat. Acad. Sci. U. S. A., doi/10.1073/pnas.1618019113. PDF SupplementalInfo SupplementalFig Sisi Li, Linda Yen, William A. Pastor, Jonathan B. Johnston, Jiamu Du, Colin Shew, Wanlu Liu, Jamie Ho, Bryan Stender, Amander T. Clark, Alma L. Burlingame, Lucia Daxinger, Dinshaw J. Patel, and Steven E. Jacobsen. (2016) Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin. Proc. Nat. Acad. Sci. U. S. A., 113:E5108-E5116. PDF Adam J. Bewick, Lexiang Ji, Chad E. Niederhuth, Eva-Maria Willing, Brigitte T. Hofmeister, Xiuling Shi, Li Wang, Zefu Lu, Nicholas A. Rohr, Benjamin Hartwig, Christiane Kiefer, Roger B. Deal, Jeremy Schmutz, Jane Grimwood, Hume Stroud, Steven E. Jacobsen, Korbinian Schneeberger, Xiaoyu Zhang, and Robert J. Schmitz. (2016) On the origin and evolutionary consequences of gene body DNA methylation. Proc. Nat. Acad. Sci. U. S. A.,113:9111-9116. PDF Martin Groth, Guillaume Moissiard, Markus Wirtz, Haifeng Wang, Carolina Garcia-Salinas, Perla A. Ramos-Parra, Sylvain Bischof, Suhua Feng, Shawn J. Cokus, Amala John, Danielle C. Smith, Jixian Zhai, Christopher J. Hale, Jeff A. Long, Ruediger Hell, Rocio I. Diaz de la Garza & Steven E. Jacobsen. (2016) MTHFD1 controls DNA methylation in Arabidopsis. Nature Communications, 7:11640. PDF SupplementalInfo Data 1 Data 2 Christopher J. Hale, Magdalena E. Potok, Jennifer Lopez, Truman Do, Ao Liu, Javier Gallego-Bartolome, Scott D. Michaels, Steven E. Jacobsen. (2016) Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. PLOS Genetics, DOI:10.1371/journal.pgen.1006092. PDF SupplementalInfo C. Jake Harris, Dylan Husmann, Wanlu Liu, Farid El Kasmi, Haifeng Wang, Ashot Papikian, William A. Pastor, Guillaume Moissiard, Ajay A. Vashisht, Jeffery L. Dang, James A. Wohlschlegel, Steven E. Jacobsen. (2016) Arabidopsis AtMORC4 and AtMORC7 Form Nuclear Bodies and Repress a Large Number of Protein-Coding Genes. PLOS Genetics, DOI:10.1371/journal.pgen.1005998. PDF SupplementalInfo William A. Pastor, Di Chen, Wanlu Liu, Rachel Kim, Anna Sahakyan, Anastasia Lukianchikov, Kathrin Plath, Steven E. Jacobsen, and Amander T. Clark. (2016) Naive Human Pluripotent Cells Feature a Methylation Landscape Devoid of Blastocyst or Germline Memory. Cell Stem Cell 18:323-329. PDF Sisi Li, Zhenlin Yang, Xuan Du, Rui Liu, Alex W. Wilkinson, Or Gozani, Steven E. Jacobsen, Dinshaw J. Patel, and Jiamu Du. (2016) Structural Basis for the Unique Multivalent Readout of Unmodified H3 Tail by Arabidopsis ORC1b BAH-PHD Cassette. Structure 24:486-494. PDF Mala Samaranayake, Pierre-Olivier Esteve, Hang Gyeong Chin, George R. Feehery, Mihika Pradhan, Steven E. Jacobsen, Michael F. Carey, and Sriharsa Pradhan. (2015) Transcription coupled DNA methylation mediated by RNA Pol II and DNMT1. Epigenetic Diagnosis & Therapy, 1:132-140. PDF Haifeng Wang, Getu Beyene, Jixian Zhai, Suhua Feng, Noah Fahlgren, Nigel J. Taylor, Rebecca Bart, James C. Carrington, Steven E. Jacobsen, and Israel Ausin. (2015) CG gene body DNA methylation changes and evolution of duplicated genes in cassava. Proc. Nat. Acad. Sci. U. S. A., 112:13729-13734 PDF Jixian Zhai, Sylvain Bischof, Haifeng Wang, Suhua Feng, Tzuu-fen Lee, Chong Teng, Xinyuan Chen, Soo Young Park, Linshan Liu, Javier Gallego-Bartolome, Wanlu Liu, Ian R. Henderson, Blake C. Meyers, Israel Ausin, and Steven E. Jacobsen. (2015) A One Precursor One siRNA Model for Pol IV-Dependent siRNA Biogenesis. Cell, 163:445-455. PDF TableS1 TableS2 TableS3