Mbd1 Is Recruited to both Methylated and Nonmethylated CpGs via Distinct DNA Binding Domains

Helle F. Jørgensen, Ittai Ben-Porath, Adrian P. Bird*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

MBD1 is a vertebrate methyl-CpG binding domain protein (MBD) that can bring about repression of methylated promoter DNA sequences. Like other MBD proteins, MBD1 localizes to nuclear foci that in mice are rich in methyl-CpG. In methyl-CpG-deficient mouse cells, however, Mbd1 remains localized to heterochromatic foci whereas other MBD proteins become dispersed in the nucleus. We find that Mbd1a, a major mouse isoform, contains a CXXC domain (CXXC-3) that binds specifically to nonmethylated CpG, suggesting an explanation for methylation-independent localization. Transfection studies demonstrate that the CXXC-3 domain indeed targets nonmethylated CpG sites in vivo. Repression of nonmethylated reporter genes depends on the CXXC-3 domain, whereas repression of methylated reporters requires the MBD. Our findings indicate that MBD1 can interpret the CpG dinucleotide as a repressive signal in vivo regardless of its methylation status.

Original languageAmerican English
Pages (from-to)3387-3395
Number of pages9
JournalMolecular and Cellular Biology
Volume24
Issue number8
DOIs
StatePublished - Apr 2004

Fingerprint

Dive into the research topics of 'Mbd1 Is Recruited to both Methylated and Nonmethylated CpGs via Distinct DNA Binding Domains'. Together they form a unique fingerprint.

Cite this