A Cell Type-Specific Class of Chromatin Loops Anchored at Large DNA Methylation Nadirs

Xiaotian Zhang; Mira Jeong; Xingfan Huang; Xue Qing David Wang; Xinyu Wang; Wanding Zhou; Muhammad S. Shamim; Haley Gore; Pamela Himadewi; Yushuai Liu; Ivan D. Bochkov; Jaime M. Reyes; Madison Doty; Yung‐Hsin Huang; Haiyoung Jung; Emily Heikamp; Aviva Presser Aiden; Wei Li; Jianzhong Su; Erez Lieberman Aiden; Margaret A. Goodell

doi:10.1016/j.molcel.2020.04.018

GenomicsMolecular CellMay 1, 2020

Peer-reviewed journal article

A Cell Type-Specific Class of Chromatin Loops Anchored at Large DNA Methylation Nadirs

Xiaotian Zhang iD, Mira Jeong iD, Xingfan Huang iD, Xue Qing David Wang iD, Xinyu Wang iD, Wanding Zhou iD, Muhammad S. Shamim iD, Haley Gore iD, Pamela Himadewi iD, Yushuai Liu iD, Ivan D. Bochkov iD, Jaime M. Reyes iD, Madison Doty iD, Yung‐Hsin Huang iD, Haiyoung Jung iD, Emily Heikamp iD, Aviva Presser Aiden iD, Wei Li iD, Jianzhong Su iD, Erez Lieberman Aiden iD, Margaret A. Goodell iD

Abstract

Higher order chromatin structure and DNA methylation are implicated in multiple developmental processes, but their relationship to cell state is unknown. Here, we found that large (~10kb) DNA methylation nadirs can form long loops connecting anchor loci that may be dozens of megabases apart, as well as interchromosomal links. The interacting loci comprise ~3.5Mb of the human genome. The data are more consistent with the formation of these loops by phase separation of the interacting loci to form a genomic subcompartment, rather than with CTCF-mediated extrusion. Interestingly, unlike previously characterized genomic subcompartments, this subcompartment is only present in particular cell types, such as stem and progenitor cells. Further, we identify one particular loop anchor that is functionally associated with maintenance of the hematopoietic stem cell state. Our work reveals that H3K27me3-marked large DNA methylation nadirs represent a novel set of very long-range loops and links associated with cellular identity.\n\nSummaryHi-C and DNA methylation analyses reveal novel chromatin loops between distant sites implicated in stem and progenitor cell function.

PDF DOI