pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene.
Genes Dev
; 21(1): 49-54, 2007 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-17210787
ABSTRACT
Genetic studies have demonstrated that Bmi1 promotes cell proliferation and stem cell self-renewal with a correlative decrease of p16(INK4a) expression. Here, we demonstrate that Polycomb genes EZH2 and BMI1 repress p16 expression in human and mouse primary cells, but not in cells deficient for pRB protein function. The p16 locus is H3K27-methylated and bound by BMI1, RING2, and SUZ12. Inactivation of pRB family proteins abolishes H3K27 methylation and disrupts BMI1, RING2, and SUZ12 binding to the p16 locus. These results suggest a model in which pRB proteins recruit PRC2 to trimethylate p16, priming the BMI1-containing PRC1L ubiquitin ligase complex to silence p16.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Histones
/
DNA Methylation
/
Cyclin-Dependent Kinase Inhibitor p16
/
Gene Silencing
/
Retinoblastoma-Like Protein p107
/
Retinoblastoma-Like Protein p130
Type of study:
Prognostic_studies
Language:
En
Journal:
Genes Dev
Journal subject:
BIOLOGIA MOLECULAR
Year:
2007
Document type:
Article
Affiliation country: