Transcriptionally active chromatin loops contain both 'active' and 'inactive' histone modifications that exhibit exclusivity at the level of nucleosome clusters
Transcriptionally active chromatin loops contain both 'active' and 'inactive' histone modifications that exhibit exclusivity at the level of nucleosome clusters
复制标题
转录活性染色质环包含“活性”和“非活性”组蛋白修饰，在核小体簇水平上表现出排他性
DOI：
10.1101/2023.09.03.555774
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Koestler S
中科院分区：
文献类型：
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作者：
Koestler S
染色质状态被认为赋予潜在的DNA序列调节功能。这可以通过组蛋白修饰和染色质组织来建立，但这些因素如何相互关联来调节基因表达尚不清楚。在这项研究中，我们已经使用超分辨率显微镜成像的Y环ofDrosophila melanogasterprimary精母细胞，这是巨大的转录活性染色质纤维，每个代表单个转录单位，是单独可分辨的核内部。我们以前发现Y环由规则的核小体簇组成，每个簇的估计中值为54个核小体，具有广泛的variation.In这项研究中，我们报告组蛋白修饰H3 K4 me 3，H3 K27 me 3和H3 K36 me 3也沿着Y环聚集，与H3 K27 me 3相比，H3 K4 me 3与弥漫染色质更相关。这些组蛋白修饰形成的结构域可以是微米长的Y环染色质的延伸，或者可以是短的交替结构域。不同的组蛋白修饰与不同大小的染色质簇和独特的形态学有关。引人注目的是，单个染色质簇几乎总是仅包含一种类型的被标记的组蛋白修饰，这表明排他性，因此在单个染色质簇的水平上进行调节。与H3 K27 me 3相比，活性标记H3 K36 me 3与主动延长RNA聚合酶II更相关，聚合酶通常出现在染色质簇外围的假定环状区域上。这些结果为理解染色质状态，染色质组织和转录调控之间的关系提供了基础-具有暂停释放动力学的潜在意义，剪接复合体的组织和染色质动力学过程中聚合酶的进展沿着基因。
Chromatin state is thought to impart regulatory function to the underlying DNA sequence. This can be established through histone modifications and chromatin organisation, but exactly how these factors relate to one another to regulate gene expression is unclear. In this study, we have used super-resolution microscopy to image the Y loops ofDrosophila melanogasterprimary spermatocytes, which are enormous transcriptionally active chromatin fibres, each representing single transcription units that are individually resolvable in the nuclear interior. We previously found that the Y loops consist of regular clusters of nucleosomes, with an estimated median of 54 nucleosomes per cluster with wide variation.In this study, we report that the histone modifications H3K4me3, H3K27me3, and H3K36me3 are also clustered along the Y loops, with H3K4me3 more associated with diffuse chromatin compared to H3K27me3. These histone modifications form domains that can be stretches of Y loop chromatin micrometres long, or can be in short alternating domains. The different histone modifications are associated with different sizes of chromatin clusters and unique morphologies. Strikingly, a single chromatin cluster almost always only contains only one type of the histone modifications that were labelled, suggesting exclusivity, and therefore regulation at the level of individual chromatin clusters. The active mark H3K36me3 is more associated with actively elongating RNA polymerase II than H3K27me3, with polymerase often appearing on what are assumed to be looping regions on the periphery of chromatin clusters.These results provide a foundation for understanding the relationship between chromatin state, chromatin organisation, and transcription regulation – with potential implications for pause-release dynamics, splicing complex organisation and chromatin dynamics during polymerase progression along a gene.