Chromatin architecture reorganization during stem cell differentiation

TLDR

Higher‑order chromatin structure is a key regulator of gene expression, yet the full extent of chromatin dynamics during mammalian development and lineage specification remains largely unknown. The authors mapped genome‑wide chromatin interactions in human embryonic stem cells and four derived lineages, revealing extensive reorganization during lineage specification. They found that while self‑associating domains remain stable, chromatin interactions within and between domains change dramatically—altering 36 % of active and inactive compartments—and that allele‑biased chromatin states correlate with widespread allelic bias in gene expression, providing a global view of chromatin dynamics across human lineages.

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.