Oct4 dependence of chromatin structure within the extended Nanog locus in ES cells (original) (raw)

  1. Dana N. Levasseur1,
  2. Jianlong Wang1,
  3. Michael O. Dorschner2,
  4. John A. Stamatoyannopoulos2, and
  5. Stuart H. Orkin1,3,4
  6. 1 Division of Hematology-Oncology, Children’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA;
  7. 2 Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
  8. 3 Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA

Abstract

Embryonic stem (ES) cells offer insight into early developmental fate decisions, and their controlled differentiation may yield vast regenerative potential. The molecular determinants supporting ES cell self-renewal are incompletely understood. The homeodomain proteins Nanog and Oct4 are essential for mouse ES cell self-renewal. Using a high-throughput approach, we discovered DNaseI hypersensitive sites and potential regulatory elements along a 160-kb region of the genome that includes_GDF3_, Dppa3, and Nanog. We analyzed gene expression, chromatin occupancy, and higher-order chromatin structure throughout this gene locus and found that expression of the reprogramming factor Oct4 is required to maintain its integrity.

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