Chromatin Architecture Reorganization During Stem Cell Differentiation

Overview

Journal Nature

Specialty Science

Date 2015 Feb 20

PMID 25693564

Citations 838

Authors

Jesse R Dixon

Inkyung Jung

Siddarth Selvaraj

Yin Shen

Jessica E Antosiewicz-Bourget

Ah Young Lee

Zhen Ye

Audrey Kim

Nisha Rajagopal

Wei Xie

Yarui Diao

Jing Liang

Huimin Zhao

Victor V Lobanenkov

Joseph R Ecker

James A Thomson

Bing Ren

Affiliations

Soon will be listed here.

Abstract

Higher-order chromatin structure is emerging as an important regulator of gene expression. Although dynamic chromatin structures have been identified in the genome, the full scope of chromatin dynamics during mammalian development and lineage specification remains to be determined. By mapping genome-wide chromatin interactions in human embryonic stem (ES) cells and four human ES-cell-derived lineages, we uncover extensive chromatin reorganization during lineage specification. We observe that although self-associating chromatin domains are stable during differentiation, chromatin interactions both within and between domains change in a striking manner, altering 36% of active and inactive chromosomal compartments throughout the genome. By integrating chromatin interaction maps with haplotype-resolved epigenome and transcriptome data sets, we find widespread allelic bias in gene expression correlated with allele-biased chromatin states of linked promoters and distal enhancers. Our results therefore provide a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.

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