Gene Set: PHESSE_TARGETS_OF_APC_AND_MBD2_UP

Standard name PHESSE_TARGETS_OF_APC_AND_MBD2_UP
Systematic name M2201
Brief description Genes up-regulated in small intestine upon loss of both APC and MBD2 [GeneID=324] [GeneID=8932].
Full description or 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18644872   Authors: Phesse TJ,Parry L,Reed KR,Ewan KB,Dale TC,Sansom OJ,Clarke AR
Exact source Table 2S: asterics
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(show 6 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform Mouse430_2
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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