Pluto Bioinformatics

GSE151577: BAHCC1 couples H3K27me3 to gene silencing and tumorigenesis via a conserved BAH module [Gw760_E2aPbx1_mouse_Rnaseq]

Bulk RNA sequencing

Tri-methylation of histone H3lysine 27 (H3K27me3) regulatestranscriptional repression, cell-fate determination and differentiation. We report that a conservedBromo-Adjacent Homology (BAH) module harbored within BAHCC1, a previouslyuncharacterized chromatin regulator,recognizes H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and ChIP-seq-basedanalyses demonstrate that direct readout of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-lysine-binding cage formed by the BAH domain, mediating co-localization of BAHCC1 and H3K27me3-marked genes.BAHCC1 is significantlyoverexpressed in human acute leukemia and biochemically, BAHCC1interacts with repressorsSAP30BPand HDAC.In acute leukemia, depletion of BAHCC1, or disruption of theBAHCC1BAH-mediated readout of H3K27me3,causesde-repressionof H3K27me3-targeted genesthat are involved in tumor suppression andcell differentiation, leading tothe suppressed tumor growth. In mice, introduction of a germ-line mutation at Bahcc1 to disrupt its H3K27me3 engagement causes postnatal lethality, supporting a role of this pathway in development. Collectively, this study unveils a novel H3K27me3-directed transduction pathway in mammal cells that relies on a conserved BAH reader, deregulation of which contributes to oncogenesis. SOURCE: Gang,Greg,Wang ( - Greg Wang UNC Lineberger Comprehensive Cancer Center

View this experiment on Pluto Bioinformatics