Regions of very low H3K27me3 partition the Drosophila genome into topological domains

Regions of very low H3K27me3 partition the Drosophila genome into topological domains
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H3K27me3 非常低的区域将果蝇基因组划分为拓扑结构域

DOI:
10.1101/072900
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发表时间:
2016
期刊:
--
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通讯作者:
El-Sharnouby S
El-Sharnouby S
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作者:
El-Sharnouby S

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现在已经明确,真核生物基因组具有共同的拓扑相关结构域(TAD)结构组织,并且越来越多的证据表明该组织在基因调控中发挥着重要作用。然而,将基因组划分为 TAD 的机制和域边界的性质仍然知之甚少。我们研究了果蝇基因组中的边界区域,发现它们可以被识别为 H3K27me3 非常低的域。全基因组 H3K27me3 配置文件分为两种状态:非常低的 H3K27me3 识别出包含管家基因及其调节因子的耗尽 (D) 结构域,例如包含组蛋白乙酰转移酶的 NSL 复合物,而包含中到高水平 H3K27me3 的结构域(富集或 E 结构域)与受调节基因相关,无论它们是活性还是非活性。 D 结构域与 TAD 的边界相关,并且富含结构蛋白的子集,特别是 Chromator、BEAF-32 和 Z4/Putzig。然而,这些蛋白质不是聚集在这些结构域的边界,而是结合在整个 H3K27me3 缺失区域,并且与管家基因的转录起始位点的相关性比与 H3K27me3 结构域边界的相关性更强。虽然我们还没有证明因果关系,但我们认为 D 结构域染色质状态(以 H3K27me3 非常低或缺失为特征,并由管家基因调节子建立)起到分离拓扑结构域的作用,从而建立了基因组的结构域。
It is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood. We have investigated boundary regions in theDrosophilagenome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing moderate-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4/Putzig. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the transcription start sites of housekeeping genes than with the H3K27me3 domain boundaries. While we have not demonstrated causality, we suggest that the D domain chromatin state, characterised by very low or absent H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome.
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