The Histone Methyltransferase Wbp7 Controls Macrophage Function through GPI Glycolipid Anchor Synthesis
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Iros Barozzi
PROVIDER: E-GEOD-30973 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description: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, MLL1M-bM-^@M-^SMLL4) 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. Gene expression profiles for bone marrow-derived macrophages (BMDM) from either Wbp7+/- (HET) or Wbp7-/- (KO). Cells were left untreated or challenged with lipopolysaccharide (LPS) for 2hrs or 4hrs. Each genotype-treatment combination were performed in triplicate.
2012-04-08 | E-GEOD-30971 | biostudies-arrayexpress
Project description: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, MLL1M-bM-^@M-^SMLL4) 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. 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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Project description:The Histone Methyltransferase Wbp7 Controls Macrophage Function through GPI Glycolipid Anchor Synthesis
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Project description:The Histone Methyltransferase Wbp7 Controls Macrophage Function through GPI Glycolipid Anchor Synthesis. [ChIP_seq]
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Project description:The Histone Methyltransferase Wbp7 Controls Macrophage Function through GPI Glycolipid Anchor Synthesis. [Expression Profile]
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