Transcriptomics

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Epigenomic comparison of distinct pluripotent stem cell states reveals a new class of enhancers with roles throughout mammalian development (RNA-seq)


ABSTRACT: Naïve 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 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 naïve-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 naïve pluripotency to a somatic regulatory program. RNA sequencing in quadruplicate of mouse embryonic stem cells and epiblast stem cells

ORGANISM(S): Mus musculus  

SUBMITTER: Daniel C Factor   Paul J Tesar  Paul J. Tesar 

PROVIDER: E-GEOD-57403 | ArrayExpress | 2014-06-04

SECONDARY ACCESSION(S): SRP041756GSE57403PRJNA246400

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

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

Factor Daniel C DC   Corradin Olivia O   Zentner Gabriel E GE   Saiakhova Alina A   Song Lingyun L   Chenoweth Josh G JG   McKay Ronald D RD   Crawford Gregory E GE   Scacheri Peter C PC   Tesar Paul J PJ  

Cell stem cell 20140601 6


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 state  ...[more]

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