Chromodomain-helicase-DNA-binding protein 2 (CHD2)

Chromodomain-helicase-DNA-binding protein 2 (CHD2) is a member of the CHD family of ATP-dependent chromatin remodelers characterized by chromodomains, an ATPase/helicase domain, and a DNA-binding module. CHD2 uses the energy from ATP hydrolysis to alter chromatin architecture, assembling chromatin into nucleosome arrays and regulating the accessibility of DNA to transcriptional machinery. It facilitates incorporation of the histone variant H3.3 at active genes and at sites of DNA repair, and coordinates with cell type-specific transcription factors (e.g., MyoD in muscle) to promote cell differentiation. CHD2 is broadly expressed, especially in brain, thyroid, ovary, and developing tissues, and its loss-of-function mutations are causative for a range of epileptic encephalopathies, neurodevelopmental disorders, and confer tumor suppressor functions in the context of DNA damage and hematopoietic homeostasis. No approved drugs specifically target CHD2, but it remains a biologically important regulatory protein relevant to developmental, neurological, and oncological diseases.

Other names

Chromodomain helicase DNA binding protein 2CHD-2ATP-dependent helicase CHD2DKFZp547I1315DKFZp781D1727DKFZp686E01200FLJ38614DEE94EEOC

Drugs (if developed) would likely function as inhibitors or modulators of ATPase activity or protein-protein/DNA interactions associated with CHD2’s chromatin remodeling activity. Mechanistically, drugs could modulate nucleosome remodeling, histone variant incorporation, or impact DNA repair pathways.