Project description:To identify the transcriptional targets of Foxa2, we treated Fh1-WT or Fh1-KO cells with either siNT or siFoxa2 and subsequent RNA-sequencing.
Project description:Comparison of the transcriptome of immortalised mouse kidney epithelial cells either wt for Fh1 or Fh1-deficient. The cells were isolated from kidneys of P5 mouse(see Frezza et al, Nature 2011). Briefly, Fh1_fl (flox) are wt for Fh1 (floxed cassette not excised), clone 1 and clone 19 are two different Fh1-deificent clones (floxed cassette excised) and Rec are clone 19 with reconstituted Fh1 expression from exogenous plasmid.
Project description:Following extensive treatment with androgen receptor (AR) pathway inhibitors, a significant number of metastatic prostate cancer develop treatment resistance, and approximately 20% of these castration-resistant prostate cancers (CRPC) transdifferentiate, at least partially, into neuroendocrine (NE) prostate cancer (NEPC).In human cancer, FOXA2 is highly expressed in most of NEPC and a small portion of CRPC patients, has been suggested as a marker of NEPC and elevated in other NE lineage cancers including SCLC. In addition, preclinical studies demonstrated that Foxa2 is required for NEPC tumor growth and metastasis in TRAMP mouse model and associated with NEPC transformation in Pten, Trp53, and Rb1 triple knockout mouse model. However, whether FOXA2 is an essential driver of NEPC, and the underlying mechanism in shaping epigenetic landscape of NEPC is largely unknown.
Project description:Following extensive treatment with androgen receptor (AR) pathway inhibitors, a significant number of metastatic prostate cancer develop treatment resistance, and approximately 20% of these castration-resistant prostate cancers (CRPC) transdifferentiate, at least partially, into neuroendocrine (NE) prostate cancer (NEPC).In human cancer, FOXA2 is highly expressed in most of NEPC and a small portion of CRPC patients, has been suggested as a marker of NEPC and elevated in other NE lineage cancers including SCLC. In addition, preclinical studies demonstrated that Foxa2 is required for NEPC tumor growth and metastasis in TRAMP mouse model and associated with NEPC transformation in Pten, Trp53, and Rb1 triple knockout mouse model. However, whether FOXA2 is an essential driver of NEPC, and the underlying mechanism in shaping epigenetic landscape of NEPC is largely unknown.
Project description:To identify candidate genes regulated by forkhead transcription factor box A2 (FOXA2) in the uterus, control and Foxa2-deleted uteri were collected at day of pseudopregnancy (DOPP) 3.5 (DOPP 0.5= vaginal plug). Microarray analysis identified differentially expressed genes in the Foxa2-deleted as compared to control uteri that are candidiate FOXA2-regulated genes in the uterus. Whole uteri (control wild type n=4; Foxa2-deleted n=4) were analyzed for differences in their transcriptome using a mouse microarray.
Project description:In each cell type the expression of genes is regulated by the action of a large number of transcription factors, but so far we have only a rudimentary knowledge of the location of the gene regulatory elements where they bind. This can now be addressed with genome-wide ChIP experiments. In a previous ChIP-chip study of USF1 and USF2 we found evidence also of binding of GABP, FOXA2 and HNF4a within the enriched regions. Here we have applied ChIP-seq for these transcription factors and identified 3064 peaks of enrichment for GABP, 7266 for FOXA2 and 18783 for HNF4a. HNF4a and FOXA2 binding was found in at least half of the regions previously identified as bound by USF2 but not USF1, showing that they frequently bind the same regulatory elements. GABP peaks were found at transcription start sites whereas 94 % of FOXA2 and 90 % of HNF4a peaks were located at other positions. We developed a method based on the high resolution achieved by ChIP-seq to accurately define TFBS within peaks, and found the predicted sites to have an elevated conservation level compared to peak centers; however the majority of bindings were not evolutionary conserved. An unexpected interaction between HNF4a and GABP was seen at TSS, with as many as 1/3 of the HNF4a positive promoters being bound also by GABP, and co-immunoprecipitations show that these factors are in the same complex in the nucleus.
Project description:In order to identify the subset of genes directly regulated by Foxa2 in the liver, we performed genome-wide location analysis. Chromatin immunoprecipitation (ChIP) samples from livers of wild type and Foxa2 liver-conditional null mice (Foxa2loxP/loxPAlfp.Cre) were hybridized to a mouse enhancer/promoter microarray with more than 36,000 elements (BCBCPromChip 5). This analysis identified 574 enhancer and promoter regions, corresponding to 484 unique genes, as occupied by Foxa2 in the adult liver.