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Status |
Public on Apr 09, 2012 |
Title |
The Histone Methyltransferase Wbp7 Controls Macrophage Function through GPI Glycolipid Anchor Synthesis. [ChIP_seq] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Histone methyltransferases catalyze site-specific deposition of methyl groups, enabling recruitment of transcriptional regulators. In mammals, trimethylation of lysine 4 in histone H3, a modification localized at the transcription start sites of active genes, is catalyzed by six enzymes (SET1a and SET1b, MLL1–MLL4) whose specific functions are largely unknown. By using a genomic approach, we found that in macrophages, MLL4 (also known as Wbp7) was required for the expression of Pigp, an essential component of the GPI-GlcNAc transferase, the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor synthesis. Impaired Pigp expression in Wbp7-/- macrophages abolished GPI anchor-dependent loading of proteins on the cell membrane. Consistently, loss of GPI-anchored CD14, the coreceptor for lipopolysaccharide (LPS) and other bacterial molecules, markedly attenuated LPS-triggered intracellular signals and gene expression changes. These data link a histone-modifying enzyme to a biosynthetic pathway and indicate a specialized biological role for Wbp7 in macrophage function and antimicrobial response.
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Overall design |
Chromatin immuno-precipitations of H3 histone try-methylated on lysine 4 followed by multiparallel sequencing performed in murine bone marrow-derive macrophages (BMDM). Experiments carried out in untreated cells as well as in cells treated for 4hrs with lipopolysaccharide (LPS), for both Wbp7+/- (HET) and Wbp7-/- (KO) mice.
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Contributor(s) |
Austenaa L, Barozzi I, Chronowska A, Termanini A, Ostuni R, Stewart F, Testa G, Natoli G |
Citation(s) |
22483804 |
Submission date |
Jul 27, 2011 |
Last update date |
May 15, 2019 |
Contact name |
Iros Barozzi |
E-mail(s) |
iros.barozzi@meduniwien.ac.at
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Organization name |
Medical University Vienna
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Street address |
Borschkegasse 8a
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City |
Vienna |
ZIP/Postal code |
1090 |
Country |
Austria |
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Platforms (1) |
GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE30973 |
The Histone Methyltransferase Wbp7 Controls Macrophage Function through GPI Glycolipid Anchor Synthesis |
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Relations |
SRA |
SRP007588 |
BioProject |
PRJNA154635 |