Epigenomic comparison reveals activation of "seed" enhancers during transition from naive to primed pluripotency.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Factor, DC; Corradin, O; Zentner, GE; Saiakhova, A; Song, L; Chenoweth, JG; McKay, RD; Crawford, GE; Scacheri, PC; Tesar, PJ

Published Date

  • June 2014

Published In

Volume / Issue

  • 14 / 6

Start / End Page

  • 854 - 863

PubMed ID

  • 24905169

Pubmed Central ID

  • 24905169

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

International Standard Serial Number (ISSN)

  • 1934-5909

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2014.05.005

Language

  • eng