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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
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Combinatorial roles of the nuclear receptor corepressor in transcription and development

K Jepsen1, O Hermanson, T M Onami

  • 1Howard Hughes Medical Institute, Department of Biology, University of California, San Diego, La Jolla 92093, USA.

Cell
|October 13, 2000
PubMed

Insights

Nuclear receptor corepressor 1 (N-CoR) is vital for metazoan development, regulating both gene repression and activation. Gene deletion studies reveal N-CoR

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Epigenetics

Background:

  • Transcriptional repression is essential for metazoan development.
  • Corepressors like N-CoR and SMRT are critical regulators.
  • N-CoR plays key roles in various developmental processes.

Purpose of the Study:

  • To investigate the role of N-CoR in transcriptional regulation during development.
  • To understand N-CoR's involvement in both repression and activation pathways.
  • To elucidate the function of corepressors and histone deacetylases in gene-specific regulation.

Main Methods:

  • Gene deletion studies in mice (N-CoR gene-deleted mice).
  • Analysis of transcriptional patterns in various tissues and cell types.
  • Investigating the role of N-CoR in nuclear receptor-mediated and REST/NRSF-mediated repression.
  • Examining N-CoR's function in retinoic acid response element activation.

Main Results:

  • N-CoR deletion caused developmental blocks in CNS, erythrocyte, and thymocyte lineages.
  • N-CoR is essential for short-term active repression by nuclear receptors and MAD.
  • N-CoR is required for a subset of long-term repression events mediated by REST/NRSF.
  • Unexpectedly, N-CoR and a deacetylase are required for transcriptional activation of a retinoic acid response element.

Conclusions:

  • N-CoR is a critical mediator of gene-specific transcriptional regulation in development.
  • Specific combinations of corepressors and histone deacetylases orchestrate gene activity.
  • These findings highlight the complex, context-dependent roles of corepressors in developmental processes.

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