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Updated: Aug 21, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
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.
Abstract:
The identification of protein components in complex networks of co-regulators responsible for the modulation of proliferation versus differentiation modes of cell growth is a major problem. We use a combination of surface enhanced laser desorption/ionization mass spectrometry, surface plasmon resonance coupled to electrospray mass spectrometry, and immunoelectromobility shift assays to identify members of the MAX/MAD family binding to a specific DNA silencer fragment involved in the regulation of transcription for the human T-cell receptor Vbeta2.2 segment. We also identify the cofactors mSin3 and N-CoR known to interact with histone deacetylases. Inhibition of deacetylase activity in Jurkat cells prevented transcription inhibitor complex formation at the Vbeta2.2 segment, suggesting that this is either directly or indirectly dependent on the presence of HDACs.
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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