Integration of external signaling pathways with the core transcriptional network in embryonic stem cells

Cell. 2008 Jun 13;133(6):1106-17. doi: 10.1016/j.cell.2008.04.043.

Abstract

Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene-expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing (ChIP-seq) to map the locations of 13 sequence-specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c-Myc, n-Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12). These factors are known to play different roles in ES-cell biology as components of the LIF and BMP signaling pathways, self-renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES-cell-specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Chromatin Immunoprecipitation
  • Embryonic Stem Cells / metabolism*
  • Gene Regulatory Networks*
  • Genome
  • Mice
  • Multiprotein Complexes
  • Signal Transduction*
  • Transcription Factors / metabolism

Substances

  • Multiprotein Complexes
  • Transcription Factors