BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis.
Journal Article (Journal Article)
Trimethylated histone H3 lysine 27 (H3K27me3) regulates gene repression, cell-fate determination and differentiation. We report that a conserved bromo-adjacent homology (BAH) module of BAHCC1 (BAHCC1BAH) 'recognizes' H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and integrated chromatin immunoprecipitation-sequencing-based analyses demonstrate that direct readout of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-L-lysine-binding 'cage' formed by BAHCC1BAH, mediating colocalization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is highly expressed in human acute leukemia and interacts with transcriptional corepressors. In leukemia, depletion of BAHCC1, or disruption of the BAHCC1BAH-H3K27me3 interaction, causes derepression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to suppression of oncogenesis. In mice, introduction of a germline mutation at Bahcc1 to disrupt its H3K27me3 engagement causes partial postnatal lethality, supporting a role in development. This study identifies an H3K27me3-directed transduction pathway in mammals that relies on a conserved BAH 'reader'.
Full Text
Duke Authors
Cited Authors
- Fan, H; Lu, J; Guo, Y; Li, D; Zhang, Z-M; Tsai, Y-H; Pi, W-C; Ahn, JH; Gong, W; Xiang, Y; Allison, DF; Geng, H; He, S; Diao, Y; Chen, W-Y; Strahl, BD; Cai, L; Song, J; Wang, GG
Published Date
- December 2020
Published In
Volume / Issue
- 52 / 12
Start / End Page
- 1384 - 1396
PubMed ID
- 33139953
Pubmed Central ID
- PMC8330957
Electronic International Standard Serial Number (EISSN)
- 1546-1718
Digital Object Identifier (DOI)
- 10.1038/s41588-020-00729-3
Language
- eng
Conference Location
- United States