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


  • eng

Conference Location

  • United States