Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023418 (
leukemia
)
93,477
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
BAH
) '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
BAH
, 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
BAH
-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'.
...
PMID:BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis. 3313 53
