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ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity

机译:ChIP-seq分析揭示了与转录活性相关的独特H3K27me3谱

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摘要

Transcriptional control is dependent on a vast network of epigenetic modifications. One epigenetic mark of particular interest is tri-methylation of lysine 27 on histone H3 (H3K27me3), which is catalysed and maintained by Polycomb Repressive Complex 2 (PRC2). Although this histone mark is studied widely, the precise relationship between its local pattern of enrichment and regulation of gene expression is currently unclear. We have used ChIP-seq to generate genome-wide maps of H3K27me3 enrichment, and have identified three enrichment profiles with distinct regulatory consequences. First, a broad domain of H3K27me3 enrichment across the body of genes corresponds to the canonical view of H3K27me3 as inhibitory to transcription. Second, a peak of enrichment around the transcription start site (TSS) is commonly associated with ‘bivalent’ genes, where H3K4me3 also marks the TSS. Finally and most surprisingly, we identified an enrichment profile with a peak in the promoter of genes that is associated with active transcription. Genes with each of these three profiles were found in different proportions in each of the cell types studied. The data analysis techniques developed here will be useful for the identification of common enrichment profiles for other histone modifications that have important consequences for transcriptional regulation.
机译:转录控制取决于表观遗传修饰的广泛网络。一个特别引起关注的表观遗传标记是组蛋白H3(H3K27me3)上赖氨酸27的三甲基化,其被Polycomb Repressive Complex 2(PRC2)催化并维持。尽管对该组蛋白标记进行了广泛研究,但目前尚不清楚其局部富集模式与基因表达调控之间的确切关系。我们已经使用ChIP-seq生成了H3K27me3富集的全基因组图谱,并确定了三种富集谱,它们具有不同的调控结果。首先,整个基因体内H3K27me3富集的一个宽域对应于H3K27me3抑制转录的规范观点。其次,转录起始位点(TSS)附近的富集峰通常与“二价”基因相关,其中H3K4me3也标记了TSS。最后,最令人惊讶的是,我们确定了一个富集谱,其启动子中的一个峰与主动转录有关。在所研究的每种细胞类型中,发现具有这三种特征的基因的比例不同。此处开发的数据分析技术将有助于识别其他丰富的组蛋白修饰的共同富集谱,这些修饰对转录调控具有重要意义。

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