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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DOI：
10.1371/journal.pone.0172725
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
White R
中科院分区：
文献类型：
--
作者：
El-Sharnouby S;Fischer B;Magbanua JP;Umans B;Flower R;Choo SW;Russell S;White R
现在已经确定真核生物基因组在拓扑相关结构域（TADs）中具有共同的结构组织，并且越来越多的证据表明这种组织在基因调控中起着重要作用。然而，将基因组划分为tad的机制和结构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，发现它们可以被鉴定为非常低的H3K27me3结构域。全基因组H3K27me3基因图谱分为两种状态；非常低的H3K27me3识别了含有家政基因及其调节因子（如含有组蛋白乙酰转移酶的NSL复合物）的贫(D)结构域，而含有中高水平H3K27me3的结构域（富集或E结构域）与受调节基因相关，无论它们是活跃还是不活跃。D结构域与TADs的边界相关，并在一些建筑蛋白中富集，特别是染色质、BEAF-32和Z4/Putzig。然而，这些蛋白不是聚集在这些结构域的边缘，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关联要比与H3K27me3结构域边界的关联强得多。虽然我们没有证明因果关系，但我们认为D结构域染色质状态，其特征是H3K27me3非常低或不存在，并由管家基因调节器建立，作用于分离拓扑结构域，从而建立基因组的结构域结构。
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 the Drosophila genome 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.