title: Solution structure of the mSin3A PAH2-Pf1 SID1 complex: a Mad1/Mxd1-like interaction disrupted by MRG15 in the Rpd3S/Sin3S complex.
abstract: Histone deacetylation constitutes an important mechanism for silencing genes. The histone-deacetylase-associated mammalian Rpd3S/Sin3S corepressor complex plays key roles in repressing aberrant gene transcription from cryptic transcription initiation sites and in mitigating RNA polymerase II progression in intragenic regions of actively transcribed genes. The Sin3 corepressor functions as a molecular adaptor linking histone deacetylases on the one hand, with the chromatin targeting subunits Pf1 and MRG15 on the other. Pf1 also functions as an adaptor by interacting with MRG15 and engaging in multivalent interactions with Sin3 targeting among other domains the two N-terminal paired amphipathic helix (PAH) domains that serve as sites of interaction with sequence-specific DNA-binding transcription factors. Here, we structurally and functionally evaluate the interaction between the PAH2 domain of mSin3A and the Sin3 interaction domain 1 (SID1) motif of Pf1 and find the structural aspects to be reminiscent of the interaction between the Mad1/Mxd1 transcription factor and Sin3. Pf1 residues within a highly conserved sequence motif immediately C-terminal to SID1 appear not to be important for the interaction with Sin3 PAH2. Unexpectedly, the MRG15 subunit competes, rather than collaborates, with Sin3 for the Pf1 segment encompassing the two conserved motifs, implying competition between two subunits for another subunit of the same chromatin-modifying complex.
authors: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208-3500, USA.
authors: Ganesan Senthil
authors: GS
authors: Kumar
authors: Tao
authors: T
authors: Xie
authors: Yongbo
authors: Y
authors: Zhang
authors: Ishwar
authors: I
authors: Radhakrishnan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins / Q000737:chemistry; D056464:Histone Deacetylase 2 / Q000737:chemistry; D018398:Homeodomain Proteins / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D012097:Repressor Proteins / Q000737:chemistry*; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000737:chemistry*; D012996:Solutions; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C501384:MAD1L1 protein, human; C470833:MORF4L1 protein, human; C079439:MXD1 protein, human; D009687:Nuclear Proteins; C430869:PHF12 protein, human; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D012996:Solutions; D014157:Transcription Factors; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2; D056264:Sin3 Histone Deacetylase and Corepressor Complex