Deficiency of Mbd2 Attenuates Wnt Signaling

Phesse, T. J., Parry, L., Reed, K. R., Ewan, K. B., Dale, T. C., Sansom, O. J. and Clarke, A. R. (2008) Deficiency of Mbd2 Attenuates Wnt Signaling. Molecular and Cellular Biology, 28(19), pp. 6094-6103. (doi: 10.1128/MCB.00539-08)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sansom, Professor Owen
• Authors: Phesse, T. J., Parry, L., Reed, K. R., Ewan, K. B., Dale, T. C., Sansom, O. J., and Clarke, A. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Molecular and Cellular Biology
• ISSN: 0270-7306