Fig. 9: Model illustrating the tumor suppressive role of CHD1 interactome.
From: Condensation-dependent interactome of a chromatin remodeler underlies tumor suppressor activities
CHD1 possesses N- and C-terminal IDR that enable its condensation around H3K4me3 nucleosomes and lncRNA (top). The CHD1 condensate incorporates histone-modifying proteins or their core components, such as ASH2L, EHMT1, and SUZ12, regulating gene expression in a cell context-specific manner. In cancer cells harboring the E1321fs mutation where CHD1 loses its IDR, the mutated CHD1 exhibits reduced condensate formation and fails to efficiently associate with H3K4me3 nucleosomes. Instead, it binds to the genome non-specifically, resulting in abnormal distribution and impaired condensation, which disrupts the recruitment of histone modifiers, leading to dysregulated transcription.
