A basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing.
Nat Chem Biol
; 16(2): 134-142, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-31819269
ABSTRACT
Recent studies have implicated the nucleosome acidic patch in the activity of ATP-dependent chromatin remodeling machines. We used a photocrosslinking-based nucleosome profiling technology (photoscanning) to identify a conserved basic motif within the catalytic subunit of ISWI remodelers, SNF2h, which engages this nucleosomal epitope. This region of SNF2h is essential for chromatin remodeling activity in a reconstituted biochemical system and in cells. Our studies suggest that the basic motif in SNF2h plays a critical role in anchoring the remodeler to the nucleosomal surface. We also examine the functional consequences of several cancer-associated histone mutations that map to the nucleosome acidic patch. Kinetic studies using physiologically relevant heterotypic nucleosomal substrates ('Janus' nucleosomes) indicate that these cancer-associated mutations can disrupt regularly spaced chromatin structure by inducing ISWI-mediated unidirectional nucleosome sliding. These results indicate a potential mechanistic link between oncogenic histones and alterations to the chromatin landscape.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomal Proteins, Non-Histone
/
Nucleosomes
/
Adenosine Triphosphatases
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Chem Biol
Journal subject:
BIOLOGIA
/
QUIMICA
Year:
2020
Type:
Article
Affiliation country:
United States