PXD021679

PXD021679 is an original dataset announced via ProteomeXchange.

Title	Identification of BAHCC1 protein interactors
Description	Trimethylation of 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 ChIP-seq-based analyses demonstrate that direct readout of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-lysine-binding ‘cage’ formed by BAHCC1BAH, mediating co-localization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is overexpressed in human acute leukemias and interacts with transcriptional co-repressors. In leukemia, depletion of BAHCC1, or disruption of the BAHCC1BAH:H3K27me3 interaction, causes de-repression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to suppression of oncogenesis. In mice, introduction of a germ-line mutation at Bahcc1 to disrupt its H3K27me3 engagement causes partial postnatal lethality, supporting a role in development. This study unveils a novel H3K27me3-directed transduction pathway in mammals that relies on a conserved BAH ‘reader’.
HostingRepository	PRIDE
AnnounceDate	2020-11-05
AnnouncementXML	Submission_2020-11-04_23:28:36.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Greg Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-25 01:35:15	ID requested
⏵ 1	2020-11-04 23:28:37	announced

Fan H, Lu J, Guo Y, Li D, Zhang ZM, Tsai YH, Pi WC, Ahn JH, Gong W, Xiang Y, Allison DF, Geng H, He S, Diao Y, Chen WY, Strahl BD, Cai L, Song J, Wang GG, BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis. Nat Genet, 52(12):1384-1396(2020) [pubmed]

submitter keyword: bahcc1, ap-ms

Greg Wang
contact affiliation	UNC-Chapel Hill
contact email	greg_wang@med.unc.edu
lab head
Greg Wang
contact affiliation	University of North Carolina at Chapel Hill
contact email	greg_wang@med.unc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021679
     1. Label: PRIDE project
     2. Name: Identification of BAHCC1 protein interactors