Transcriptomics

Dataset Information

122

Dynamics of MBD2 deposition across methylated DNA regions during malignant transformation of human mammary epithelial cells (3)


ABSTRACT: DNA methylation is thought to induce a transcriptional silencing through the combination of two mechanisms: the repulsion of transcriptional activators that do not recognize their binding sites when methylated, and the recruitment of transcriptional repressors that specifically bind methylated DNA. Methyl CpG Binding Domain proteins MeCP2, MBD1 and MBD2 belong to the latter category. However, the exact contribution of each protein in the DNA methylation dependent transcriptional repression occurring during development and diseases remains elusive. Here we present MBD2 ChIPseq data generated from the endogenous protein in an isogenic cellular model of human mammary oncogenic transformation. In immortalized or transformed cells, MBD2 was found in one fourth of methylated regions and associated with transcriptional silencing. Depletion of MBD2 induces upregulations of genes bound by MBD2 and methylated in their transcriptional start site regions. MBD2 was partially redistributed on methylated DNA during oncogenic transformation, independently of DNA methylation changes. Genes downregulated during this transformation preferentially gained MBD2 binding sites on their promoter. Depletion of MBD2 in transformed cells induced the upregulation of some of these repressed genes, independently of the strategy used for the abrogation of oncosuppressive barriers. Our data confirm that MBD2 is a major interpret of DNA methylation, and show an unreported dynamic in this interpretation during oncogenic transformation. MBD2 ChIP and input, Methylated DNA precipitation and input, in HMEC-hTERT and HMLER cell lines

ORGANISM(S): Homo sapiens  

SUBMITTER: Guillaume Devailly   Mélodie Grandin  Anne-Pierre Morel  Laury Perriaud  Patrick Mehlen  Robert Dante  Alain Puisieux  Jean-Guy Delcros  Pauline Mathot 

PROVIDER: E-GEOD-63235 | ArrayExpress | 2015-06-17

SECONDARY ACCESSION(S): GSE63235PRJNA267113

REPOSITORIES: GEO, ArrayExpress

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Publications

Dynamics of MBD2 deposition across methylated DNA regions during malignant transformation of human mammary epithelial cells.

Devailly Guillaume G   Grandin Mélodie M   Perriaud Laury L   Mathot Pauline P   Delcros Jean-Guy JG   Bidet Yannick Y   Morel Anne-Pierre AP   Bignon Jean-Yves JY   Puisieux Alain A   Mehlen Patrick P   Dante Robert R  

Nucleic acids research 20150524 12


DNA methylation is thought to induce transcriptional silencing through the combination of two mechanisms: the repulsion of transcriptional activators unable to bind their target sites when methylated, and the recruitment of transcriptional repressors with specific affinity for methylated DNA. The Methyl CpG Binding Domain proteins MeCP2, MBD1 and MBD2 belong to the latter category. Here, we present MBD2 ChIPseq data obtained from the endogenous MBD2 in an isogenic cellular model of oncogenic tra  ...[more]

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