The Developmental Regulator Protein Gon4l Associates with Protein YY1, Co-repressor Sin3a, and Histone Deacetylase 1 and Mediates Transcriptional Repression

Ping Lu; Isaiah L Hankel; Bruce S Hostager; Julie A Swartzendruber; Ann D Friedman; Janet L Brenton; Paul B Rothman; John D Colgan

doi:10.1074/jbc.M110.133603

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The Developmental Regulator Protein Gon4l Associates with Protein YY1, Co-repressor Sin3a, and Histone Deacetylase 1 and Mediates Transcriptional Repression

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The Developmental Regulator Protein Gon4l Associates with Protein YY1, Co-repressor Sin3a, and Histone Deacetylase 1 and Mediates Transcriptional Repression

Ping Lu, Isaiah L Hankel, Bruce S Hostager, Julie A Swartzendruber, Ann D Friedman, Janet L Brenton, Paul B Rothman and John D Colgan

The Journal of biological chemistry, Vol.286(20), pp.18311-18319

05/20/2011

DOI: 10.1074/jbc.M110.133603

PMCID: PMC3093903

PMID: 21454521

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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.

Gene Regulation

Cell Differentiation

Transcription Factors

Co-repressor Transcription

B Cell Development

Histone Deacetylase

Details

Title: Subtitle: The Developmental Regulator Protein Gon4l Associates with Protein YY1, Co-repressor Sin3a, and Histone Deacetylase 1 and Mediates Transcriptional Repression
Creators: Ping Lu
Isaiah L Hankel - Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
Bruce S Hostager - the Departments of
Julie A Swartzendruber - the Departments of
Ann D Friedman - the Departments of
Janet L Brenton - the Departments of
Paul B Rothman - From the
John D Colgan - From the
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.286(20), pp.18311-18319
DOI: 10.1074/jbc.M110.133603
PMID: 21454521
PMCID: PMC3093903
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: R01AI067489 / National Institutes of Health
Alternative title: Gon4l Associates with YY1 and Sin3a/HDAC1
Language: English
Date published: 05/20/2011
Academic Unit: Microbiology and Immunology; Anatomy and Cell Biology; Immunology; Internal Medicine
Record Identifier: 9984025561102771

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