期刊
CELL STEM CELL
卷 14, 期 6, 页码 854-863出版社
CELL PRESS
DOI: 10.1016/j.stem.2014.05.005
关键词
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资金
- NIH [R01HD056369, R01CA160356]
- New York Stem Cell Foundation
- Mt. Sinai Health Care Foundation
- Genomics and Cytometry core facilities of the Case Comprehensive Cancer Center [P30CA043703]
- CWRU Cellular and Molecular Biology training grant [T32GM008056]
Naive mouse embryonic stem cells (mESCs) and primed epiblast stem cells (mEpiSCs) represent successive snapshots of pluripotency during embryogenesis. Using transcriptomic and epigenomic mapping we show that a small fraction of transcripts are differentially expressed between mESCs and mEpiSCs and that these genes show expected changes in chromatin at their promoters and enhancers. Unexpectedly, the cis-regulatory circuitry of genes that are expressed at identical levels between these cell states also differs dramatically. In mESCs, these genes are associated with dominant proximal enhancers and dormant distal enhancers, which we term seed enhancers. In mEpiSCs, the naive-dominant enhancers are lost, and the seed enhancers take up primary transcriptional control. Seed enhancers have increased sequence conservation and show preferential usage in downstream somatic tissues, often expanding into super enhancers. We propose that seed enhancers ensure proper enhancer utilization and transcriptional fidelity as mammalian cells transition from naive pluripotency to a somatic regulatory program.
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