Engagement of DNA and H3K27me3 by the CBX8 chromodomain drives chromatin association.
Nucleic Acids Res
; 47(5): 2289-2305, 2019 03 18.
Article
in En
| MEDLINE
| ID: mdl-30597065
ABSTRACT
Polycomb repressive complex 1 (PRC1) is critical for mediating gene repression during development and adult stem cell maintenance. Five CBX proteins, CBX2,4,6,7,8, form mutually exclusive PRC1 complexes and are thought to play a role in the association of PRC1 with chromatin. Specifically, the N-terminal chromodomain (CD) in the CBX proteins is thought to mediate specific targeting to methylated histones. For CBX8, however, the chromodomain has demonstrated weak affinity and specificity for methylated histones in vitro, leaving doubt as to its role in CBX8 chromatin association. Here, we investigate the function of the CBX8 CD in vitro and in vivo. We find that the CD is in fact a major driver of CBX8 chromatin association and determine that this is driven by both histone and previously unrecognized DNA binding activity. We characterize the structural basis of histone and DNA binding and determine how they integrate on multiple levels. Notably, we find that the chromatin environment is critical in determining the ultimate function of the CD in CBX8 association.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
Chromatin
/
Histones
/
Polycomb Repressive Complex 1
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2019
Document type:
Article