6VIL

Crystal structure of mouse BAHCC1 BAH domain in complex with H3K27me3

Summary for 6VIL

• Entry DOI: 10.2210/pdb6vil/pdb
• Descriptor: BAH and coiled-coil domain-containing protein 1, Histone H3.1 (2 entities in total)
• Functional Keywords: structural protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 12
• Total formula weight: 154155.88

Authors

Song, J.,Lu, J. (deposition date: 2020-01-13, release date: 2020-09-16, Last modification date: 2023-10-11)

Primary citation

Fan, H.,Lu, J.,Guo, Y.,Li, D.,Zhang, Z.M.,Tsai, Y.H.,Pi, W.C.,Ahn, J.H.,Gong, W.,Xiang, Y.,Allison, D.F.,Geng, H.,He, S.,Diao, Y.,Chen, W.Y.,Strahl, B.D.,Cai, L.,Song, J.,Wang, G.G.
BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis.
Nat.Genet., 52:1384-1396, 2020

PubMed Abstract: 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 (BAHCC1) '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 BAHCC1, 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 BAHCC1-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'.

PubMed: 33139953
DOI: 10.1038/s41588-020-00729-3

Experimental method

X-RAY DIFFRACTION (3.301 Å)