| Literature DB >> 32386543 |
Xiaotian Zhang1, Mira Jeong2, Xingfan Huang3, Xue Qing Wang4, Xinyu Wang5, Wanding Zhou4, Muhammad S Shamim6, Haley Gore4, Pamela Himadewi4, Yushuai Liu4, Ivan D Bochkov7, Jaime Reyes8, Madison Doty9, Yung-Hsin Huang10, Haiyoung Jung11, Emily Heikamp12, Aviva Presser Aiden13, Wei Li14, Jianzhong Su5, Erez Lieberman Aiden15, Margaret A Goodell16.
Abstract
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.Entities:
Keywords: 3D genomics; CpG; DNA methylation; DNA methylation canyon; Polycomb; chromosomal looping; hematopoietic; self-renewal; stem cells
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Year: 2020 PMID： 32386543 PMCID： PMC7357281 DOI： 10.1016/j.molcel.2020.04.018
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970