Chromodomain-helicase-DNA-binding protein 1 (CHD1)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) is an ATP-dependent chromatin remodeler and member of the SNF2-like family ATPases, characterized by two tandem chromodomains, an ATPase (helicase) domain, and a DNA-binding SANT/SLIDE domain[1][2][3][4]. CHD1 modulates chromatin structure by repositioning nucleosomes in an ATP-dependent manner, facilitating accessible (euchromatic) states and regulating transcription[1][2][4]. CHD1 is pivotal for embryonic stem cell pluripotency, lineage-specific differentiation, and maintenance of transcriptional boundaries between activating (H3K4me3) and elongation (H3K36me3) histone marks[2]. It serves a crucial role in DNA damage response by promoting open chromatin and facilitating homologous recombination-mediated repair[2]. In disease, CHD1 mutations or loss are recurrent in certain cancers (notably prostate cancer) and are associated with neurodevelopmental phenotypes. To date, CHD1 itself is not directly drugged clinically, but its loss or dysregulation is under investigation as a biomarker and potential therapeutic vulnerability[2][4][5]. The enzyme functions predominantly as a monomer, catalyzing chromatin assembly via processive generation of regularly spaced nucleosomes, requiring ATP and histone chaperones such as NAP1[1].

Other names

CHD1CHD-1ATP-dependent helicase CHD1PILBOSchromodomain-helicase-DNA-binding protein 1

ATPase-dependent chromatin remodeling (targeted molecules would aim to modulate the ATP-dependent nucleosome sliding, assembly, or eviction activity) Indirect modulation via upstream regulation (possible future strategies might include inhibiting protein-protein or protein-DNA interactions)