Chromatin architecture reorganization during stem cell differentiation

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 and Bing Ren ()
Additional contact information
Jesse R. Dixon: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Inkyung Jung: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Siddarth Selvaraj: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Yin Shen: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Jessica E. Antosiewicz-Bourget: The Morgridge Institute for Research, 309 North Orchard Street
Ah Young Lee: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Zhen Ye: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Audrey Kim: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Nisha Rajagopal: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Wei Xie: Tsinghua University–Peking University Center for Life Sciences, School of Life Sciences, Tsinghua University
Yarui Diao: Ludwig Institute for Cancer Research, 9500 Gilman Drive
Jing Liang: University of Illinois at Urbana-Champaign
Huimin Zhao: University of Illinois at Urbana-Champaign
Victor V. Lobanenkov: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Twinbrook I NIAID Facility, Room 1417, 5640 Fishers Lane, Rockville, Maryland 20852, USA
Joseph R. Ecker: Howard Hughes Medical Institute, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
James A. Thomson: The Morgridge Institute for Research, 309 North Orchard Street
Bing Ren: Ludwig Institute for Cancer Research, 9500 Gilman Drive

Nature, 2015, vol. 518, issue 7539, 331-336

Abstract: 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.

Date: 2015
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DOI: 10.1038/nature14222

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