Chromatin architecture reorganization during stem cell differentiation.
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.
Duke Scholars
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Related Subject Headings
- Reproducibility of Results
- Promoter Regions, Genetic
- Humans
- General Science & Technology
- Gene Regulatory Networks
- Epigenomics
- Epigenesis, Genetic
- Enhancer Elements, Genetic
- Embryonic Stem Cells
- Chromatin Assembly and Disassembly
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Reproducibility of Results
- Promoter Regions, Genetic
- Humans
- General Science & Technology
- Gene Regulatory Networks
- Epigenomics
- Epigenesis, Genetic
- Enhancer Elements, Genetic
- Embryonic Stem Cells
- Chromatin Assembly and Disassembly