title: The developmental regulator protein Gon4l associates with protein YY1, co-repressor Sin3a, and histone deacetylase 1 and mediates transcriptional repression.
abstract: Genetic studies involving zebrafish and mice have demonstrated that the protein Gon4l (Gon4-like) is essential for hematopoiesis. These studies also suggested that Gon4l regulates gene expression during hematopoietic development, yet the biochemical function of Gon4l has not been defined. Here, we describe the identification of factors that interact with Gon4l and may cooperate with this protein to regulate gene expression. As predicted by polypeptide sequence conservation, Gon4l interacted and co-localized with the DNA-binding protein YY1 (Yin Yang 1). Density gradient sedimentation analysis of protein lysates from mouse M12 B cells showed that Gon4l and YY1 co-sediment with the transcriptional co-repressor Sin3a and its functional partner histone deacetylase (HDAC) 1. Consistent with these results, immunoprecipitation studies showed that Gon4l associates with Sin3a, HDAC1, and YY1 as a part of complexes that form in M12 cells. Sequential immunoprecipitation studies demonstrated that Gon4l, YY1, Sin3a, and HDAC1 could all associate as components of a single complex and that a conserved domain spanning the central portion of Gon4l was required for formation of this complex. When targeted to DNA, Gon4l repressed the activity of a nearby promoter, which correlated with the ability to interact with Sin3a and HDAC1. Our data suggest that Sin3a, HDAC1, and YY1 are co-factors for Gon4l and that Gon4l may function as a platform for the assembly of complexes that regulate gene expression.
authors: Interdisciplinary Immunology Graduate Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors: Ping
authors: P
authors: Lu
authors: Isaiah L
authors: IL
authors: Hankel
authors: Bruce S
authors: BS
authors: Hostager
authors: Julie A
authors: JA
authors: Swartzendruber
authors: Ann D
authors: AD
authors: Friedman
authors: Janet L
authors: JL
authors: Brenton
authors: Paul B
authors: PB
authors: Rothman
authors: John D
authors: JD
authors: Colgan
mesh_terms: D000818:Animals; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C514882:GON4L protein, human; D046912:Multiprotein Complexes; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D056264:Sin3 Histone Deacetylase and Corepressor Complex