The histone variant MacroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1 Journal Article

Authors: Hussey, K. M.; Chen, H.; Yang, C.; Park, E.; Hah, N.; Erdjument-Bromage, H.; Tempst, P.; Gamble, M. J.; Kraus, W. L.
Article Title: The histone variant MacroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1
Abstract: MacroH2A1 is a histone variant harboring an ~25-kDa carboxyl-terminal macrodomain. Due to its enrichment on the inactive X chromosome, macroH2A1 was thought to play a role in transcriptional repression. However, recent studies have shown that macroH2A1 occupies autosomal chromatin and regulates genes in a context-specific manner. The macrodomain may play a role in the modulation of gene expression outcomes via physical interactions with effector proteins, which may depend on the ability of the macrodomain to bind NAD+ metabolite ligands. Here, we identify proline, glutamic acid, and leucine-rich protein 1 (PELP1), a chromatin-associated factor and transcriptional coregulator, as a ligand-independent macrodomain-interacting factor. We used chromatin immunoprecipitation coupled with tiling microarrays (ChIP-chip) to determine the genomic localization of PELP1 in MCF-7 human breast cancer cells. We find that PELP1 genomic localization is highly correlated with that of macroH2A1. Additionally, PELP1 positively correlates with heterochromatic chromatin marks and negatively correlates with active transcription marks, much like macroH2A1. MacroH2A1 specifically recruits PELP1 to the promoters of macroH2A1 target genes, but macroH2A1 occupancy occurs independent of PELP1. This recruitment allows macroH2A1 and PELP1 to cooperatively regulate gene expression outcomes. © 2014, American Society for Microbiology.
Keywords: controlled study; human cell; protein function; gene expression; protein protein interaction; transcription regulation; histone; chromatin immunoprecipitation; glutamic acid; histone h2a; gene location; heterochromatin; proline; human; priority journal; article
Journal Title: Molecular and Cellular Biology
Volume: 34
Issue: 13
ISSN: 0270-7306
Publisher: American Society for Microbiology  
Date Published: 2014-07-01
Start Page: 2437
End Page: 2449
Language: English
DOI: 10.1128/mcb.01315-13
PROVIDER: scopus
PMCID: PMC4054320
PUBMED: 24752897
Notes: Mol. Cell. Biol. -- Export Date: 8 July 2014 -- CODEN: MCEBD -- Source: Scopus
Altmetric Score
MSK Authors
  1. Paul J Tempst
    312 Tempst