title: Repression of transcription at the human T-cell receptor Vbeta2.2 segment is mediated by a MAX/MAD/mSin3 complex acting as a scaffold for HDAC activity.
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.
authors.affiliation: Unité INSERM 462, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Font
authors.forename: Myriam
authors.initials: M
authors.lastname: Cubizolles
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.forename: Lucien
authors.initials: L
authors.lastname: Cazes
authors.forename: Virginie
authors.initials: V
authors.lastname: Brenac
authors.forename: François
authors.initials: F
authors.lastname: Sigaux
authors.forename: Malcolm
authors.initials: M
authors.lastname: Buckle
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012097:Repressor Proteins; D006655:Histone Deacetylases