Preferential binding of the methyl-CpG binding domain protein 2 at methylated transcriptional start site regions.
Détails
ID Serval
serval:BIB_1C5894F8C31C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Preferential binding of the methyl-CpG binding domain protein 2 at methylated transcriptional start site regions.
Périodique
Epigenetics
ISSN
1559-2308 (Electronic)
ISSN-L
1559-2294
Statut éditorial
Publié
Date de publication
11/2011
Volume
6
Numéro
11
Pages
x
Langue
anglais
Résumé
Methyl-CpG Binding Domain (MBD) proteins are thought to be key molecules in the interpretation of DNA methylation signals leading to gene silencing through recruitment of chromatin remodeling complexes. In cancer, the MBD-family member, MBD2, may be primarily involved in the repression of genes exhibiting methylated CpG at their 5' end. Here we ask whether MBD2 randomly associates methylated sequences, producing chance effects on transcription, or exhibits a more specific recognition of some methylated regions. Using chromatin and DNA immunoprecipitation, we analyzed MBD2 and RNA polymerase II deposition and DNA methylation in HeLa cells on arrays representing 25,500 promoter regions. This first whole-genome mapping revealed the preferential localization of MBD2 near transcription start sites (TSSs), within the region analyzed, 7.5 kb upstream through 2.45 kb downstream of 5' transcription start sites. Probe by probe analysis correlated MBD2 deposition and DNA methylation. Motif analysis did not reveal specific sequence motifs; however, CCG and CGC sequences seem to be overrepresented. Nonrandom association (multiple correspondence analysis, p < 0.0001) between silent genes, DNA methylation and MBD2 binding was observed. The association between MBD2 binding and transcriptional repression weakened as the distance between binding site and TSS increased, suggesting that MBD2 represses transcriptional initiation. This hypothesis may represent a functional explanation for the preferential binding of MBD2 at methyl-CpG in TSS regions.
Pubmed
Web of science
Création de la notice
28/11/2011 10:20
Dernière modification de la notice
20/08/2019 13:52