Repression of transcription at the human T-cell receptor Vbeta2.2 segment is mediated by a MAX/MAD/mSin3 complex

Marie-Pierre Font1, Myriam Cubizolles, Hervé Dombret

  • 1Unité INSERM 462, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.

Insights

Researchers identified protein complexes regulating cell growth, specifically MAX/MAD family members, mSin3, and N-CoR, binding to a DNA silencer. This binding is dependent on histone deacetylase (HDAC) activity.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cellular Regulation

Background:

  • Identifying protein regulators in complex cellular networks is challenging.
  • Understanding cell proliferation versus differentiation is crucial for development and disease.

Purpose of the Study:

  • To identify protein components of co-regulatory networks involved in cell growth.
  • To investigate the role of histone deacetylases in transcriptional regulation of the T-cell receptor Vbeta2.2 segment.

Main Methods:

  • Surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS)
  • Surface plasmon resonance coupled to electrospray mass spectrometry (SPR-ESI-MS)
  • Immunoelectromobility shift assays (IEMSA)

Main Results:

  • Identified MAX/MAD family members binding to a specific DNA silencer fragment.
  • Identified cofactors mSin3 and N-CoR, known histone deacetylase (HDAC) interactors.
  • Inhibition of deacetylase activity prevented transcription inhibitor complex formation.

Conclusions:

  • The formation of transcription inhibitor complexes at the Vbeta2.2 segment is dependent on HDAC activity.
  • This study elucidates key protein interactions in cell growth regulation.

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