title: Deficiency of Mbd2 attenuates Wnt signaling.
abstract: We have previously shown that deficiency of the methyl binding domain protein Mbd2 dramatically reduces adenoma burden on an Apc(Min/+) background. To investigate the mechanism underlying this phenomenon, we have determined the effect of Mbd2 deficiency upon the phenotypes imposed by the conditional deletion of Apc in the small intestine. Microarray analysis demonstrated a partial suppression of the Wnt pathway in the absence of Mbd2. Mbd2 deficiency also influenced one immediate cellular consequence of Apc loss, with normalization of Paneth cell positioning. From a mechanistic perspective, we show that deficiency of Mbd2 elevates levels of the known Wnt target Lect2, and we confirm here that Mbd2 binds the Lect2 promoter in association with NuRD. Furthermore, we show that Lect2 is capable of functioning as a Wnt pathway repressor. These results therefore provide a mechanistic basis for the epigenetic control of adenoma formation mediated through Mbd2.
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom.
authors.forename: Toby J
authors.initials: TJ
authors.lastname: Phesse
authors.forename: Lee
authors.initials: L
authors.lastname: Parry
authors.forename: Karen R
authors.initials: KR
authors.lastname: Reed
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Ewan
authors.forename: Trevor C
authors.initials: TC
authors.lastname: Dale
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.forename: Alan R
authors.initials: AR
authors.lastname: Clarke
mesh_terms: D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D017491:Genes, APC; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007421:Intestine, Small / Q000473:pathology; D019879:Paneth Cells / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C491213:Lect2 protein, mouse; C489326:Mbd2 protein, mouse; D051153:Wnt Proteins