ENL reads histone β-hydroxybutyrylation to modulate gene transcription
Ontology highlight
ABSTRACT:
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Hepatocyte
DISEASE(S): Disease Free
SUBMITTER: 
Feng Zhai
LAB HEAD: Guijin Zhai
PROVIDER: PXD051689 | Pride | 2024-06-26
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| H3K4-1.raw | Raw | |||
| H3K4-2.raw | Raw | |||
| H3K4-3.raw | Raw | |||
| H3K4me3-1.raw | Raw | |||
| H3K4me3-2.raw | Raw |
Items per page: 5 1 - 5 of 14 |
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Project description:Histone modifications are typically recognized by chromatin-binding protein modules (referred to as 'readers') to mediate fundamental processes such as transcription. Lysine β-hydroxybutyrylation (Kbhb) is a new type of histone mark that couples metabolism to gene expression. However, the readers that prefer histone Kbhb remain elusive. This knowledge gap should be filled in order to reveal the molecular mechanism of this epigenetic regulation. Herein, we developed a chemical proteomic approach, relying upon multivalent photoaffinity probes to capture binders of the mark, and identified ENL as a novel target of H3K9bhb. Biochemical studies and CUT&Tag analysis further suggested that ENL favorably binds to H3K9bhb, and co-localizes with it on promoter regions to modulate gene expression. Notably, disrupting the interaction between H3K9bhb and ENL via structure-based mutation led to the suppressed expression of genes such MYC that drive cell proliferation. Together, our work offered a chemoproteomics approach and identified ENL as a novel histone β-hydroxybutyrylation effector that regulates gene transcription, providing new insight into the regulation mechanism and function of histone Kbhb.
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