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  The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers

Greulich, F., Wierer, M., Mechtidou, A., Gonzalez-Garcia, O., & Uhlenhaut, N. H. (2021). The glucocorticoid receptor recruits the COMPASS complex to regulate inflammatory transcription at macrophage enhancers. Cell Reports, 34(6): 108742. doi:10.1016/j.celrep.2021.108742.

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 Creators:
Greulich, Franziska1, Author
Wierer, Michael2, Author              
Mechtidou, Aikaterini1, Author
Gonzalez-Garcia, Omar1, Author
Uhlenhaut, N. Henriette1, Author
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1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: HISTONE H3; BINDING PROTEIN; METHYLTRANSFERASE COMPLEX; SACCHAROMYCES-CEREVISIAE; CHROMATIN ACCESSIBILITY; MOLECULAR REGULATION; SET1 COMPLEX; PHD FINGER; R PACKAGE; GENECell Biology;
 Abstract: Glucocorticoids (GCs) are effective anti-inflammatory drugs; yet, their mechanisms of action are poorly understood. GCs bind to the glucocorticoid receptor (GR), a ligand-gated transcription factor controlling gene expression in numerous cell types. Here, we characterize GR's protein interactome and find the SETD1A (SET domain containing 1A)/COMPASS (complex of proteins associated with Set1) histone H3 lysine 4 (H3K4) methyltransferase complex highly enriched in activated mouse macrophages. We show that SETD1A/COMPASS is recruited by GR to specific cis-regulatory elements, coinciding with H3K4 methylation dynamics at subsets of sites, upon treatment with lipopolysaccharide (LPS) and GCs. By chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq, we identify subsets of GR target loci that display SETD1A occupancy, H3K4 mono-, di-, or tri-methylation patterns, and transcriptional changes. However, our data on methylation status and COMPASS recruitment suggest that SETD1A has additional transcriptional functions. Setd1a loss-of-function studies reveal that SETD1A/COMPASS is required for GR-controlled transcription of subsets of macrophage target genes. We demonstrate that the SETD1A/COMPASS complex cooperates with GR to mediate anti-inflammatory effects.

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Language(s): eng - English
 Dates: 2021-02
 Publication Status: Published online
 Pages: 23
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 Table of Contents: -
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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 34 (6) Sequence Number: 108742 Start / End Page: - Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247