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.

• Authors: Kristine M Hussey, Hongshan Chen, Christine Yang, Eugene Park, Nasun Hah, Hediye Erdjument-Bromage, Paul Tempst, Matthew J Gamble, W Lee Kraus
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 34 Issue 13 Pg. 2437-49 (Jul 2014) ISSN: 1098-5549 [Electronic] United States
• PMID: 24752897 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Chromatin
• Co-Repressor Proteins
• Histones
• PELP1 protein, human
• RNA, Small Interfering
• Receptors, Estrogen
• Transcription Factors
• macroH2A histone
• Doxycycline

Topics

• Anti-Bacterial Agents (pharmacology)
• Cell Line, Tumor
• Chromatin (chemistry, genetics)
• Chromatin Immunoprecipitation
• Co-Repressor Proteins (biosynthesis, genetics)
• Doxycycline (pharmacology)
• Gene Expression Regulation (genetics)
• Histones (genetics, metabolism)
• Humans
• MCF-7 Cells
• Oligonucleotide Array Sequence Analysis
• Promoter Regions, Genetic
• Protein Structure, Tertiary
• RNA Interference
• RNA, Small Interfering
• Receptors, Estrogen (genetics)
• Signal Transduction (genetics)
• Transcription Factors (biosynthesis, genetics)
• Transcription, Genetic