ADP-ribose polymers localized on Ctcf-Parp1-Dnmt1 complex prevent methylation of Ctcf target sites.
Biochem J
; 441(2): 645-52, 2012 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-21985173
ABSTRACT
PARylation [poly(ADP-ribosyl)ation] is involved in the maintenance of genomic methylation patterns through its control of Dnmt1 [DNA (cytosine-5)-methyltransferase 1] activity. Our previous findings indicated that Ctcf (CCCTC-binding factor) may be an important player in key events whereby PARylation controls the unmethylated status of some CpG-rich regions. Ctcf is able to activate Parp1 [poly(ADP-ribose) polymerase 1], which ADP-ribosylates itself and, in turn, inhibits DNA methylation via non-covalent interaction between its ADP-ribose polymers and Dnmt1. By such a mechanism, Ctcf may preserve the epigenetic pattern at promoters of important housekeeping genes. The results of the present study showed Dnmt1 as a new protein partner of Ctcf. Moreover, we show that Ctcf forms a complex with Dnmt1 and PARylated Parp1 at specific Ctcf target sequences and that PARylation is responsible for the maintenance of the unmethylated status of some Ctcf-bound CpGs. We suggest a mechanism by which Parp1, tethered and activated at specific DNA target sites by Ctcf, preserves their methylation-free status.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Poli Adenosina Difosfato Ribose
/
Proteínas Repressoras
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Poli(ADP-Ribose) Polimerases
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DNA (Citosina-5-)-Metiltransferases
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália