Context-specific functions of chromatin remodellers in development and disease.
Nat Rev Genet
; 25(5): 340-361, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38001317
ABSTRACT
Chromatin remodellers were once thought to be highly redundant and nonspecific in their actions. However, recent human genetic studies demonstrate remarkable biological specificity and dosage sensitivity of the thirty-two adenosine triphosphate (ATP)-dependent chromatin remodellers encoded in the human genome. Mutations in remodellers produce many human developmental disorders and cancers, motivating efforts to investigate their distinct functions in biologically relevant settings. Exquisitely specific biological functions seem to be an emergent property in mammals, and in many cases are based on the combinatorial assembly of subunits and the generation of stable, composite surfaces. Critical interactions between remodelling complex subunits, the nucleosome and other transcriptional regulators are now being defined from structural and biochemical studies. In addition, in vivo analyses of remodellers at relevant genetic loci have provided minute-by-minute insights into their dynamics. These studies are proposing new models for the determinants of remodeller localization and function on chromatin.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Nat Rev Genet
Assunto da revista:
GENETICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos