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HNF4alpha P1 and P2 isoforms regulate different gene networks in the colorectal cancer cell line Caco2/15.

ABSTRACT: The nuclear receptor HNF4alpha is a master regulator of gene transcription in intestinal epithelial cells where P1 and P2 isoforms are expressed. HNF4alpha has been associated with colorectal cancer where its role remains controverisal since both tumor suppressor and oncogene characteristics have been observed. Evidences gathered from mouse models suggested however that this controversy on HNF4alpha function in colorectal cancer could be explained by the different functions of its two isoforms classes. In order to clarify this hypothesis in a human context, we downregulated the expression of HNF4alpha P1 or P2 isoforms using isoforms specific shRNA in the colorectal cancer cell line Caco2/15. Transcriptomic data were obtained by RNA-seq from these shRNA cell populations and compared to a non-target shRNA control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE106378 | GEO | 2018/06/26

REPOSITORIES: GEO

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HNF4alpha P1 and P2 isoforms regulate different gene networks in the colorectal cancer cell line Caco2/15.

Project description:HNF4alpha P1 and P2 isoforms regulate different gene networks in the colorectal cancer cell line Caco2/15.

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Developmentally regulated isoform of HNF4α reprograms the adult liver

Project description:Hepatocyte Nuclear Factor 4α (HNF4α), master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2). P1-HNF4α but not P2-HNF4α is expressed in normal adult liver in fed conditions. Both P1- and P2-HNF4α are expressed in fetal liver. P2-HNF4α expression is increased in fasted conditions, high fat diet, alcoholic liver and liver cancer. To determine the target genes of the P1- and P2-HNF4α isoforms, we compared P2-HNF4α-expressing exon swap mice (a7HMZ) to wildtype (WT) male mice. Liver ChIP-seq samples were taken at 10:30 AM (ZT 3.5)

2023-05-10 | GSE231538 | GEO

Developmentally regulated isoform of HNF4α reprograms the adult liver

Project description:Hepatocyte Nuclear Factor 4α (HNF4α), master regulator of hepatocyte differentiation, is regulated by two promoters (P1 and P2). P1-HNF4α but not P2-HNF4α is expressed in normal adult liver while both P1- and P2-HNF4α are expressed in fetal liver and liver cancer. To determine the physiological function of the HNF4α isoforms, we compared P2-HNF4α-expressing exon swap mice to wildtype (WT) using RNA-seq, ChIP-seq, proteomics, protein binding microarrays (PBMs) and metabolomics. P2-HNF4α orchestrates a distinct transcriptomic and metabolomic profile.

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Differential role of HNF4α isoforms in colitis and colitis-associated colon cancer

Project description:Hepatocyte nuclear factor 4alpha (HNF4α) is a nuclear receptor with an emerging role in the gut. While HNF4α has been implicated in colitis and colon cancer in humans, deciphering its functional role is complicated by the existence of two promoters (P1 and P2) in theHNF4A gene that drive the expression of multiple isoforms in the adult intestine. In this study we investigate the roles of P1- and P2-driven HNF4α under conditions of homeostasis, colitis and colitis-associated colon cancer (CAC). P1- and P2-HNF4α are differentially expressed in the differentiated and proliferative compartments of the normal colonic crypt, respectively. Expression profiling of untreated exon swap mice suggests distinct functions of the isoforms that were corroborated in migration and ion transport assays.

2016-05-23 | GSE47731 | GEO

From mouse to humans: detecting preventing vaccination targets associated to breast cancer stem cells. Exon-level analysis

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ib101206 - proteome data analysis

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2018-03-19 | PXD003287 | Pride

Sex-dependent and HNF4alpha-dependent Mouse Liver Gene Expression

Project description:A series of dual-channel gene expression profiles obtained using Rosetta/Agilent Whole Mouse Genome oligonucleotide microarrays, 4 x 44K format, was used to identify sex-dependent and HNF4alpha-dependent differences in gene expression in adult mouse liver. This series is comprised of four sex-genotype combinations: adult male wild-type liver (M-WT), adult female wild-type liver (F-WT), adult male liver-specific HNF4alpha knockout liver (M-KO) and adult female liver-specific HNF4alpha knockout liver (F-KO). Four pools, each comprised of 4 randomly selected individual liver RNAs, were prepared for each sex-genotype combination. The pools were paired randomly to generate 4 separate experimental comparisons: M-WT:F-WT (first array comparison), M-WT:M-KO (second array comparison), F-WT:F-KO (third array comparison), and M-KO:F-KO (fourth array comparison). A total of 4994 HNF4alpha-dependent genes were identified, of which ~1000 fewer genes responded to the loss of HNF4alpha in female liver as compared to male liver. Moreover, 90% of the genes showing sex-specific expression in the liver were shown to lose sex specificity in HNF4alpha-deficient liver. Keywords: genetic knockout and sex response

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Gene expression data from livers of 3-month-old HNF4alpha knockout mice

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Targets of transduced Foxa and Hnf4alpha proteins in mouse embryonic fibroblasts (MEFs).

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Gene expression data from livers of 3-month-old HNF4alpha knockout mice

Project description:HNF4alpha is a master regulator of hepatic differentiation. In this study, HNF4alpha was deleted in adult mice using a Cre-LoxP system where Cre recombinase was delivered using an AAV8 virus. Total RNA was isolated from the livers of HNF4alpha-floxed mice (mixed backgournd) treated with either Control Virus or Cre-carrying virus at 3 months of age.

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