Transcription profiling of mouse HNF4 null mutant colon vs. control colons

ABSTRACT: Background and Aims: HNF4? is a nuclear hormone receptor transcription factor that has been shown to be required for hepatocyte differentiation and development of the liver. It has also been implicated in regulating expression of genes that act in the epithelium of the lower gastrointestinal tract. This implied that HNF4? might be required for development of the gut. Methods: We generated mouse embryos in which Hnf4? was ablated in the epithelial cells of the fetal colon using Cre-loxP technology. Embryos were examined using a combination of histology, immunohistochemistry, gene array and RT-PCR, and chromatin immunoprecipitation analyses to define the consequence of loss of HNF4? on colon development. Results: Embryos could be generated until E18.5 that lacked HNF4? in their colon. Although, early stages of colonic development occurred, HNF4? null colons failed to form normal crypts. In addition, goblet cell maturation was perturbed and expression of an array of genes that encode proteins with diverse roles in colon function was disrupted. Several genes whose expression in the colon was dependent on HNF4? contained HNF4?–binding sites sequences within putative transcriptional regulatory regions and a subset of these sites were occupied by HNF4? in vivo. Conclusion: HNF4? is a transcription factor that is essential for development of the mammalian colon, regulates goblet cell maturation and is required for expression of genes that control normal colon function and epithelial cell differentiation. Experiment Overall Design: COMPARISON OF 3 MUTANT TO 2 CONTROL COLONS.

ORGANISM(S): Mus musculus

SUBMITTER: Stephen Duncan 

PROVIDER: E-GEOD-3116 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress