大型DNA甲基化最低点锚定染色质环，维持造血干细胞特性。
Large DNA Methylation Nadirs Anchor Chromatin Loops Maintaining Hematopoietic Stem Cell Identity.
作者信息
Zhang Xiaotian, Jeong Mira, Huang Xingfan, Wang Xue Qing, Wang Xinyu, Zhou Wanding, Shamim Muhammad S, Gore Haley, Himadewi Pamela, Liu Yushuai, Bochkov Ivan D, Reyes Jaime, Doty Madison, Huang Yung-Hsin, Jung Haiyoung, Heikamp Emily, Aiden Aviva Presser, Li Wei, Su Jianzhong, Aiden Erez Lieberman, Goodell Margaret A
机构信息
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
出版信息
Mol Cell. 2020 May 7;78(3):506-521.e6. doi: 10.1016/j.molcel.2020.04.018.
Higher-order chromatin structure and DNA methylation are implicated in multiple developmental processes, but their relationship to cell state is unknown. Here, we find that large (>7.3 kb) DNA methylation nadirs (termed "grand canyons") can form long loops connecting anchor loci that may be dozens of megabases (Mb) apart, as well as inter-chromosomal links. The interacting loci cover a total of ∼3.5 Mb of the human genome. The strongest interactions are associated with repressive marks made by the Polycomb complex and are diminished upon EZH2 inhibitor treatment. The data are suggestive of the formation of these loops by interactions between repressive elements in the loci, forming a genomic subcompartment, rather than by cohesion/CTCF-mediated extrusion. Interestingly, unlike previously characterized subcompartments, these interactions are present only in particular cell types, such as stem and progenitor cells. Our work reveals that H3K27me3-marked large DNA methylation grand canyons represent a set of very-long-range loops associated with cellular identity.
高阶染色质结构和DNA甲基化与多个发育过程相关，但它们与细胞状态的关系尚不清楚。在这里，我们发现大型（>7.3 kb）DNA甲基化最低点（称为“大峡谷”）可形成长环，连接可能相隔数十兆碱基（Mb）的锚定基因座，以及染色体间连接。相互作用的基因座总共覆盖了约350万个碱基对的人类基因组。最强的相互作用与多梳复合体产生的抑制性标记相关，并且在EZH2抑制剂处理后减弱。数据表明，这些环是由基因座中的抑制元件之间的相互作用形成的，形成了一个基因组亚区室，而不是通过黏连蛋白/CTCF介导的挤压形成。有趣的是，与先前表征的亚区室不同，这些相互作用仅存在于特定的细胞类型中，如干细胞和祖细胞。我们的工作表明，H3K27me3标记的大型DNA甲基化大峡谷代表了一组与细胞身份相关的超远距离环。
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