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MBD2 Is Required for Correct Spatial Gene Expression in the Gut ^,

Jennifer Berger,¹ Owen Sansom,^2, Alan Clarke,² and Adrian Bird^1*

Wellcome Trust Centre for Cell Biology, Edinburgh University, The King's Buildings, Edinburgh EH9 3JR, United Kingdom,¹ Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom²

Received 29 October 2006/ Returned for modification 30 November 2006/ Accepted 6 March 2007

Gene expression in the gut is segmentally regulated, but little is known of the molecular origin of patterning. Analysis of gene expression in colons from mice lacking the methyl-CpG binding repressor MBD2 revealed frequent activation of genes that are normally only expressed in the exocrine pancreas and duodenum. Reduced DNA methylation activated the same gene set in the colon. No significant differences in DNA methylation between the colon and duodenum were detected, but MBD2 was significantly more abundant in the colon. The relevance of MBD2 concentration was tested in a human colon cancer cell line. Depletion of MBD2 was again found to activate exocrine pancreatic genes. Gene activation in this cell culture model was accompanied by loss of promoter-bound MBD2 and increased histone acetylation. The results suggest that modulation of MBD2 during gut development establishes a region-specific gene expression pattern that is essential for establishing correct segmental character.

Published ahead of print on 12 March 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: CR-UK Beatson Institute for Cancer Research, Glasgow G6 11BD, United Kingdom.