Epigenetic priming of a Pre-B Cell-Specific enhancer through binding of Sox2 and Foxd3 at the ESC stage

Daniel Liber, Renae Domaschenz, Per Henrik Holmqvist, Luca Mazzarella, Andrew Georgiou, Marion Leleu, Amanda G. Fisher, Patricia A. Labosky, Niall Dillon

Research output: Contribution to journalArticlepeer-review

Abstract

Modifications to the core histones are thought to contribute to ESC pluripotency by priming tissuespecific promoters and enhancers for later activation. However, it is unclear how these marks are targeted in ESCs and maintained during differentiation. Here, we show that the ESC factor Sox2 targets H3K4 methylation to monovalent and bivalent domains. In ESCs, Sox2 contributes to the formation of a monovalent mark at an enhancer in the pro/pre-B cell-specific λ5-VpreB1 locus. Binding of Foxd3 suppresses intergenic transcription of the enhancer and surrounding sequences. In pro-B cells, enhancer activity is dependent on the Sox and Fox binding sites, and the enhancer is bound by Sox4, which is required for efficient expression of λ5. Our results lead us to propose a factor relay model whereby ESC factors establish active epigenetic marks at tissue specific elements before being replaced by cell type-specific factors as cells differentiate.

Original languageEnglish
Pages (from-to)114-126
Number of pages13
JournalCell Stem Cell
Volume7
Issue number1
DOIs
Publication statusPublished - Jul 2010

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

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