MBD2 is required for correct spatial gene expression in the gut.
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.
Berger
Jennifer
J
Wellcome Trust Centre for Cell Biology, Edinburgh University, The King's Buildings, Mayfield Road, Edinburgh, United Kingdom.
Sansom
Owen
O
Clarke
Alan
A
Bird
Adrian
A
D000818:Animals; D019521:Body Patterning; D045744:Cell Line, Tumor; D003106:Colon / Q000502:physiology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004386:Duodenum / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009024:Morphogenesis; D010179:Pancreas / Q000502:physiology; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C489326:Mbd2 protein, mouse; D034741:RNA, Small Interfering; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases