Chromatinremodeler

Chromatin remodelers are multi-subunit protein complexes that use the energy from ATP hydrolysis to alter the structure and positioning of nucleosomes, thereby changing the accessibility of DNA. By repositioning, evicting, or exchanging histones, they regulate the print of genetic information access for processes such as transcription, replication, and DNA repair. They do not modify histones directly but change chromatin architecture to influence downstream chromatin regulators and factors.

The major families are defined by their catalytic ATPase subunits and include the SWI/SNF family (ATPases BRG1/BRM, SMARCA4/SMARCA2), the ISWI family (SNF2H/SNF2L, SMARCA5/SMARCA1), the CHD family (examples include CHD1, CHD4), and the INO80 family (INO80 and related remodelers). The SWR1 family, which uses SRCAP or related proteins, specializes in exchanging histone variants such as H2A.Z. Remodelers assemble as large complexes with core ATPases and accessory proteins that determine targeting to specific genomic loci and the type of remodeling performed.

Mechanistically, the ATPase motor drives translocation of DNA around the histone core, producing nucleosome sliding, eviction, or histone variant exchange. The activity is directed by the accompanying subunits, which read chromatin context and interact with transcription factors, histone marks, and chromatin modifiers.

Biological roles are broad, including regulation of gene expression programs during development and differentiation, maintenance of genome stability, and coordination of DNA replication and repair. Alterations in chromatin remodeling genes are linked to cancers and developmental disorders, making remodelers important both for understanding biology and as potential therapeutic targets.