Chromatin architecture reorganization during stem cell differentiation

作者：Jesse R. Dixon, Inkyung Jung, Siddarth Selvaraj, Yin Shen, Jessica 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 Alexander Thomson, Bing Ren · 发表于：Nature · 年份：2015 · DOI：10.1038/nature14222 · 被引用次数：1866 · 研究领域：Genomics and Chromatin Dynamics、Epigenetics and DNA Methylation、Chromosomal and Genetic Variations

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. An analysis of genome-wide chromatin interactions during human embryonic stem cell differentiation reveals changes in chromatic organization and simultaneously identifies allele-resolved chromatin structure and differences in gene expression during differentiation. Higher-order chromatin structures are among the factors influencing gene express...