Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells

Marion Dejosez, Stuart S. Levine, Garrett M. Frampton, Warren A. Whyte, Sabrina A. Stratton, Michelle C. Barton, Preethi H. Gunaratne, Richard A. Young, Thomas P. Zwaka

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Self-renewing embryonic stem (ES) cells have an exceptional need for timely biomass production, yet the transcriptional control mechanisms responsible for meeting this requirement are largely unknown. We report here that Ronin (Thap11), which is essential for the self-renewal of ES cells, binds with its transcriptional coregulator, Hcf-1, to a highly conserved enhancer element that previously lacked a recognized binding factor. The subset of genes bound by Ronin/Hcf-1 function primarily in transcription initiation, mRNA splicing, and cell metabolism; genes involved in cell signaling and cell development are conspicuously underrepresented in this target gene repertoire. Although Ronin/Hcf-1 represses the expression of some target genes, its activity at promoter sites more often leads to the up-regulation of genes essential to protein biosynthesis and energy production. We propose that Ronin/Hcf-1 controls a genetic program that contributes to the unimpeded growth of ES cells.

Original languageEnglish (US)
Pages (from-to)1479-1484
Number of pages6
JournalGenes and Development
Volume24
Issue number14
DOIs
StatePublished - Jul 15 2010
Externally publishedYes

Keywords

  • Cell growth
  • Pluripotency
  • Stem cells
  • Transcriptional control

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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