Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
Genome Res. 2011 Feb;21(2):216-26. doi: 10.1101/gr.114348.110. Epub 2010 Dec 22.
The Polycomb group (PcG) and Trithorax group (TrxG) of proteins are required for stable and heritable maintenance of repressed and active gene expression states. Their antagonistic function on gene control, repression for PcG and activity for TrxG, is mediated by binding to chromatin and subsequent epigenetic modification of target loci. Despite our broad knowledge about composition and enzymatic activities of the protein complexes involved, our understanding still lacks important mechanistic detail and a comprehensive view on target genes. In this study we use an extensive data set of ChIP-seq, RNA-seq, and genome-wide detection of transcription start sites (TSSs) to identify and analyze thousands of binding sites for the PcG proteins and Trithorax from a Drosophila S2 cell line. In addition of finding a preference for stalled promoter regions of annotated genes, we uncover many intergenic PcG binding sites coinciding with nonannotated TSSs. Interestingly, this set includes previously unknown promoters for primary transcripts of microRNA genes, thereby expanding the scope of Polycomb control to noncoding RNAs essential for development, apoptosis, and growth.
多梳蛋白（PcG）和三价组蛋白（TrxG）蛋白对于抑制和激活基因表达状态的稳定和可遗传维持是必需的。它们在基因调控中的拮抗功能，PcG 的抑制和 TrxG 的激活，是通过与染色质结合和随后对靶基因座的表观遗传修饰来介导的。尽管我们对涉及的蛋白质复合物的组成和酶活性有广泛的了解，但我们的理解仍然缺乏重要的机制细节和对靶基因的全面了解。在这项研究中，我们使用了一个广泛的 ChIP-seq、RNA-seq 和全基因组转录起始位点（TSS）检测数据集，从 Drosophila S2 细胞系中鉴定和分析了数千个 PcG 蛋白和 Trithorax 的结合位点。除了发现对注释基因的停滞启动子区域的偏好之外，我们还发现了许多与非注释 TSS 重合的基因间 PcG 结合位点。有趣的是，这一组包括以前未知的 miRNA 基因初级转录物的启动子，从而将 Polycomb 控制扩展到对发育、细胞凋亡和生长至关重要的非编码 RNA。
