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Nature. 2015 Feb 19;518(7539):331-6. doi: 10.1038/nature14222.

Chromatin architecture reorganization during stem cell differentiation.

Author information

  • 11] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA [2] Medical Scientist Training Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
  • 2Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA.
  • 31] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA [2] Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
  • 4The Morgridge Institute for Research, 309 North Orchard Street, Madison, Wisconsin 53715, USA.
  • 5Tsinghua University-Peking University Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 6Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
  • 7Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Twinbrook I NIAID Facility, Room 1417, 5640 Fishers Lane, Rockville, Maryland 20852, USA.
  • 8Howard Hughes Medical Institute, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
  • 91] The Morgridge Institute for Research, 309 North Orchard Street, Madison, Wisconsin 53715, USA [2] Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA [3] Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, California 93106, USA.
  • 101] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA [2] University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA.

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.

PMID:
25693564
[PubMed - indexed for MEDLINE]
PMCID:
PMC4515363
Free PMC Article
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