Human Gene Set: GSE30971_2H_VS_4H_LPS_STIM_MACROPHAGE_WBP7_HET_DN
Standard name
GSE30971_2H_VS_4H_LPS_STIM_MACROPHAGE_WBP7_HET_DN
Systematic name
M8725
Brief description
Genes down-regulated in bone marrow-derived macrophages with heterozygous MLL4 [GeneID=9757] knockout: 2h LPS versus 4h LPS.
Full description or abstract
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.
