Polycomb preferentially targets stalled promoters of coding and noncoding transcripts

Polycomb preferentially targets stalled promoters of coding and noncoding transcripts
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DOI:
10.1101/gr.114348.110
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发表时间:
2011-02-01
期刊:
影响因子:
7
通讯作者:
Paro, Renato
Paro, Renato
中科院分区:
生物学1区
文献类型:
--
作者:
Enderle, Daniel;Beisel, Christian;Paro, Renato

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多梳组(PcG)和三胸组(TrxG)的蛋白质是所需的稳定和可遗传的抑制和活性基因表达状态的维持。它们对基因控制、PcG抑制和TrxG活性的拮抗功能通过与染色质结合和随后的靶基因座的表观遗传修饰介导。尽管我们对所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看法。在这项研究中,我们使用了广泛的数据集ChIP-seq,RNA-seq和全基因组转录起始位点(TSS)检测,以确定和分析PcG蛋白和果蝇S2细胞系Trithorax的数千个结合位点。除了找到一个偏好的停滞的启动子区域的注释基因,我们发现许多基因间的PcG结合位点与nonannotated TSS相一致。有趣的是,这一组包括以前未知的microRNA基因初级转录物的启动子,从而将Polycomb控制的范围扩大到对发育,凋亡和生长至关重要的非编码RNA。
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.