Chromatin remodeling complex (CRC)

Chromatin remodeling complexes are multi-subunit molecular machines that utilize the energy of ATP hydrolysis to alter the structure and positioning of nucleosomes, thereby regulating access to the underlying DNA (Clapier et al., 2017, Nature Reviews Molecular Cell Biology). These complexes, including the SWI/SNF (BAF), ISWI, CHD, and INO80 families, are essential for fundamental cellular processes such as gene transcription, DNA repair, and cell cycle control (Hargreaves & Crabtree, 2011, Cell Research). Mutations in these complexes are highly prevalent in human diseases; for instance, subunits of the SWI/SNF complex are mutated in approximately 20% of all human cancers (Kadoch & Crabtree, 2015, Science). In oncology, these complexes are targeted through the inhibition of their catalytic ATPase subunits or the use of proteolysis-targeting chimeras (PROTACs) to induce degradation of specific subunits (St. Pierre & Kadoch, 2017, Nature Medicine). Therapeutic strategies often exploit synthetic lethal relationships, such as targeting the SMARCA2 subunit in cancers harboring SMARCA4 mutations (Wilson & Roberts, 2011, Nature Reviews Cancer). Despite their therapeutic potential, the broad regulatory roles of these complexes present challenges regarding systemic toxicity and the maintenance of normal gene expression patterns (Centore et al., 2020, Nature Chemical Biology).

Other names

ATP-dependent chromatin remodeling complexChromatin remodelerSWI/SNF complexBAF complexPBAF complexISWI complexCHD complexINO80 complex

Inhibition of ATPase catalytic activity, degradation of complex subunits via PROTACs, and competitive inhibition of bromodomain-mediated chromatin binding.