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

  1. Thomas P. Zwaka1,2,8
  1. 1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA;
  2. 2Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;
  3. 3Department of Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
  4. 4Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;
  5. 5Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;
  6. 6Program in Genes and Development, Center for Stem Cell and Development Biology, Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
  7. 7Department of Biology and Biochemistry, University of Houston, Houston, Texas 77004, USA

    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.

    Keywords

    Footnotes

    • Received April 7, 2010.
    • Accepted May 27, 2010.

    Freely available online through the Genes & Development Open Access option.

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