H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication.
Nucleic Acids Res
; 45(1): 169-180, 2017 01 09.
Article
em En
| MEDLINE
| ID: mdl-27679476
ABSTRACT
DNA replication is tightly regulated to occur once and only once per cell cycle. How chromatin, the physiological substrate of DNA replication machinery, regulates DNA replication remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d regulates DNA replication in eukaryotic cells. Depletion of Kdm4d results in defects in DNA replication, which can be rescued by the expression of H3K9M, a histone H3 mutant transgene that reverses the effect of Kdm4d on H3K9 methylation. Kdm4d interacts with replication proteins, and its recruitment to DNA replication origins depends on the two pre-replicative complex components (origin recognition complex [ORC] and minichromosome maintenance [MCM] complex). Depletion of Kdm4d impairs the recruitment of Cdc45, proliferating cell nuclear antigen (PCNA), and polymerase δ, but not ORC and MCM proteins. These results demonstrate a novel mechanism by which Kdm4d regulates DNA replication by reducing the H3K9me3 level to facilitate formation of pre-initiative complex.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Histonas
/
Replicação do DNA
/
Histona Desmetilases com o Domínio Jumonji
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos