<br>生物信息学筛选揭示了果蝇组蛋白基因座的 hox 和染色质重塑因子,BMC Genetics

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生物信息学筛选揭示了果蝇组蛋白基因座的 hox 和染色质重塑因子
BMC Genetics Pub Date : 2023-09-21 , DOI: 10.1186/s12863-023-01147-0
Lauren J Hodkinson ₁ , Connor Smith ₂ , H Skye Comstra ₂ , Bukola A Ajani ₂ , Eric H Albanese ₂ , Kawsar Arsalan ₂ , Alvaro Perez Daisson ₂ , Katherine B Forrest ₂ , Elijah H Fox ₂ , Matthew R Guerette ₂ , Samia Khan ₂ , Madeleine P Koenig ₂ , Shivani Lam ₂ , Ava S Lewandowski ₂ , Lauren J Mahoney ₂ , Nasserallah Manai ₂ , JonCarlo Miglay ₂ , Blake A Miller ₂ , Olivia Milloway ₂ , Nhi Ngo ₂ , Vu D Ngo ₂ , Nicole F Oey ₂ , Tanya A Punjani ₂ , HaoMin SiMa ₂ , Hollis Zeng ₂ , Casey A Schmidt ₂ , Leila E Rieder ₂

Affiliation

细胞通过严格的时间和定量控制来协调组蛋白生物发生。为了有效调节组蛋白生物发生，重复的黑腹果蝇复制依赖性组蛋白基因排列并聚集在单个基因座上。调节因子集中在称为组蛋白基因座体（HLB）的核体中，该基因座围绕基因座形成。从历史上看，HLB 因子在很大程度上是偶然发现的，很少有已知与 DNA 直接相互作用。因此，目前尚不清楚组蛋白基因如何专门靶向独特和协调的调节。为了扩展已知 HLB 因子的列表，我们通过将 27 个独特因子的 30 个公开可用的 ChIP 数据集映射到果蝇组蛋白基因阵列来执行基于候选者的筛选。我们确定了新的转录因子候选者，包括果蝇 Hox 蛋白 Ultrabithorax （Ubx）、Abdominal-A （Abd-A）和 Abdominal-B （Abd-B），表明这些因素影响身体计划形态发生的新途径。此外，我们确定了靶向组蛋白基因阵列的其他六个因子：JIL-1、激素样受体 78 （Hr78）、雌性不育同源长亚型（1）（fs（1）h）以及一般转录因子 TBP 相关因子 1 （TAF-1）、转录因子 IIB （TFIIB）和转录因子 IIF （TFIIF）。我们的基础筛选为未来研究可能影响组蛋白生物发生的因素提供了几个候选者。此外，我们的研究强调了强大的公开数据集库，可以作为一种初步筛选技术进行挖掘。

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A bioinformatics screen reveals hox and chromatin remodeling factors at the Drosophila histone locus

Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets of 27 unique factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B), suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other factors that target the histone gene array: JIL-1, hormone-like receptor 78 (Hr78), the long isoform of female sterile homeotic (1) (fs(1)h) as well as the general transcription factors TBP associated factor 1 (TAF-1), Transcription Factor IIB (TFIIB), and Transcription Factor IIF (TFIIF). Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.

更新日期：2023-09-21

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