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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

The HOX homeodomain proteins block CBP histone acetyltransferase activity

W F Shen1, K Krishnan, H J Lawrence

  • 1Department of Medicine, VA Medical Center and University of California, San Francisco, California 94121, USA. wfshen@itsa.ucsf.edu

Molecular and Cellular Biology
|October 5, 2001
PubMed

Insights

HOX proteins interact with CBP/p300, but surprisingly inhibit DNA binding and transcription. These HOX proteins may function as transcription repressors by inhibiting CBP/p300 activity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Transcription Regulation

Background:

  • HOX proteins are crucial developmental regulators.
  • PBC proteins are known HOX cofactors, enhancing DNA binding and specificity.
  • HOX proteins exhibit limited activity in transcription assays, with few identified targets.

Purpose of the Study:

  • To investigate interactions between HOX proteins and CBP/p300.
  • To elucidate the functional consequences of HOX-CBP/p300 binding on HOX protein activity.
  • To explore novel roles for HOX proteins in gene regulation.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • DNA binding assays to assess complex formation.
  • Reporter gene assays to measure transcriptional activity.
  • In vitro and in vivo assays to evaluate histone acetyltransferase (HAT) activity inhibition.

Main Results:

  • All tested HOX proteins bind to CBP and p300, primarily through their homeodomain.
  • CBP/p300 binding inhibits HOX protein DNA binding.
  • HOX proteins inhibit CBP/p300 histone acetyltransferase (HAT) activity.
  • CBP/p300 fails to potentiate HOX-induced gene activation.

Conclusions:

  • HOX proteins interact with CBP/p300, but this interaction is inhibitory rather than cooperative for DNA binding.
  • HOX proteins may function as transcription repressors by inhibiting CBP/p300 HAT activity.
  • Alternative models for HOX function, potentially independent of CBP HAT, are proposed.

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