Genome-wide occupancy profiling of Foxa2 in iHepC [ChIL-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE302220 | GEO | 2025/08/19
REPOSITORIES: GEO
Similar Datasets
Project description:We investigated which genomic regions the transcription factor Hnf4a, ectopically introduced to induce hepatocyte-like cells (iHepCs) from MEFs through direct reprogramming, binds to in iHepCs.
2025-08-19 | GSE282869 | GEO
Project description:HNF4a and FOXA2 are two liver enriched transcription factors that have been shown capable of reprogramming fibroblasts into hepatocyte-like cells. However to date it is not yet understood how these master regulators, expressed in both embryonic and adult liver contribute to the transcriptional changes necessary for hepatocyte maturation during development. Consequently we undertook to identify binding sites and target genes for HNF4a and FOXA2 in the embryonic liver. A comparison of embryonic and adult liver TF binding patterns revealed widespread differentiation-dependent genome occupancy associated with changes in target gene expression during liver development.
2014-08-31 | GSE54520 | GEO
Project description:Understanding how silent genes can be competent for activation provides insight into development as well as cellular reprogramming and pathogenesis. We performed genomic location analysis of the pioneer transcription factor FoxA in the adult liver and found that about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. Virtually all of the FoxA-bound silent sites are within extended conserved sequences, suggesting possible function. Such sequences are enriched in motifs for transcriptional repressors, including for Rfx1. We found one such target site containing functional FoxA and Rfx1 sites is a cryptic enhancer 7 kb downstream of the Cdx2 gene, the latter being an effector of esophageal metaplasia. Indeed, Rfx1 sites restrict transcriptional activation by FoxA at the +7 kb Cdx2 element. Furthermore, Rfx1 expression in the esophageal epithelium becomes extinguished during its metaplastic progression to carcinoma. We propose that motif analysis of other transcription factors bound to silent genes can reveal unanticipated regulatory networks that provide insights into reprogramming and oncogenic progression. We analyzed FOXA2 occupancy in a mouse liver sample. We ran three competitive hybridizations: (i) FOXA2 vs IgG, (ii) FOXA2 vs input, and (iii) IgG vs input.
2011-07-18 | E-GEOD-23551 | biostudies-arrayexpress
Project description:The aim of this study was to test, in vivo, if Foxa2 inhibits HNF6-mediated transcription in the liver. We utilized hepatocyte-specific gene ablation of Foxa2 and the Mouse PromoterChip BCBC 3.0 and Mouse PancChip 5.0 cDNA microarrays to investigate HNF6 binding to its target promoters in vivo in the presence or absence of Foxa2. For the mouse promoter microarray analysis, chromatin immunoprecipitation using anti-HNF6 antibodies was performed on chromatin isolated from Foxa2loxP/loxP Alfp.Cre and control mouse livers. Along with sheared genomic DNA (common reference), the immunoprecipitated DNA was amplified, labeled and hybridized to the Mouse PromoterChip BCBC 3.0. For microarray analysis of gene expression, liver RNAs were isolated from three Foxa2loxP/loxP Alfp.Cre and three control mice. RNAs were reverse transcribed, labeled, and hybridized to the Mouse PancChip 5.0. Overall, our studies demonstrate that HNF6 binds to and regulates its target promoters in vivo in the presence and absence of Foxa2 and that the expression levels of HNF6 targets are not influenced by Foxa2.
2007-09-14 | E-CBIL-36 | biostudies-arrayexpress
Project description:FOXA (Forkhead Box Protein A) family proteins function as pioneer transcription factors by loosening the compact chromatin structure and facilitating access for other transcription factors. The role of FOXA1 has been intensively studied in normal prostate epithelial cells and the adenocarcinoma subtype of prostate cancer (PCa) where it acts as a critical pioneer factor for the chromatin binding of androgen receptor (AR). Recent studies have indicated the emergence of FOXA2 as an adaptive response to AR signaling inhibition, particularly in prostate tumors that have undergone lineage reprogramming to a neuroendocrine PCa subtype. However, the molecular basis for this transition from FOXA1 to FOXA2 and its role in regulating the development of PCa lineage plasticity remains unclear. In this study, we show that FOXA2 binds to distinct chromatin regions in multiple AR-null PCa models with different molecular subtypes and that its binding is dependent on an epigenetic factor, LSD1. More importantly, we demonstrate that FOXA2 can function as a major pioneer factor of JUN and govern the chromatin binding of AP-1 complex in PCa exhibiting lineage plasticity. Mechanistically, differential reprogramming of JUN activates lineage-specific super-enhancers that may promote PCa progression by enhancing cell state transitions to multiple lineages. Overall, our study reveals a pivotal function of the LSD1-FOXA2 axis in rewiring AP-1 to induce differential transcriptional reprogramming required for PCa lineage plasticity.
2024-04-22 | GSE232554 | GEO
Project description:FOXA (Forkhead Box Protein A) family proteins function as pioneer transcription factors by loosening the compact chromatin structure and facilitating access for other transcription factors. The role of FOXA1 has been intensively studied in normal prostate epithelial cells and the adenocarcinoma subtype of prostate cancer (PCa) where it acts as a critical pioneer factor for the chromatin binding of androgen receptor (AR). Recent studies have indicated the emergence of FOXA2 as an adaptive response to AR signaling inhibition, particularly in prostate tumors that have undergone lineage reprogramming to a neuroendocrine PCa subtype. However, the molecular basis for this transition from FOXA1 to FOXA2 and its role in regulating the development of PCa lineage plasticity remains unclear. In this study, we show that FOXA2 binds to distinct chromatin regions in multiple AR-null PCa models with different molecular subtypes and that its binding is dependent on an epigenetic factor, LSD1. More importantly, we demonstrate that FOXA2 can function as a major pioneer factor of JUN and govern the chromatin binding of AP-1 complex in PCa exhibiting lineage plasticity. Mechanistically, differential reprogramming of JUN activates lineage-specific super-enhancers that may promote PCa progression by enhancing cell state transitions to multiple lineages. Overall, our study reveals a pivotal function of the LSD1-FOXA2 axis in rewiring AP-1 to induce differential transcriptional reprogramming required for PCa lineage plasticity.
2024-04-22 | GSE232552 | GEO
Project description:FOXA (Forkhead Box Protein A) family proteins function as pioneer transcription factors by loosening the compact chromatin structure and facilitating access for other transcription factors. The role of FOXA1 has been intensively studied in normal prostate epithelial cells and the adenocarcinoma subtype of prostate cancer (PCa) where it acts as a critical pioneer factor for the chromatin binding of androgen receptor (AR). Recent studies have indicated the emergence of FOXA2 as an adaptive response to AR signaling inhibition, particularly in prostate tumors that have undergone lineage reprogramming to a neuroendocrine PCa subtype. However, the molecular basis for this transition from FOXA1 to FOXA2 and its role in regulating the development of PCa lineage plasticity remains unclear. In this study, we show that FOXA2 binds to distinct chromatin regions in multiple AR-null PCa models with different molecular subtypes and that its binding is dependent on an epigenetic factor, LSD1. More importantly, we demonstrate that FOXA2 can function as a major pioneer factor of JUN and govern the chromatin binding of AP-1 complex in PCa exhibiting lineage plasticity. Mechanistically, differential reprogramming of JUN activates lineage-specific super-enhancers that may promote PCa progression by enhancing cell state transitions to multiple lineages. Overall, our study reveals a pivotal function of the LSD1-FOXA2 axis in rewiring AP-1 to induce differential transcriptional reprogramming required for PCa lineage plasticity.
2024-04-22 | GSE232553 | GEO
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.
2025-06-12 | PXD061127 | Pride
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.
2025-06-12 | PXD061080 | Pride
Project description:Liver firbrosis model of hepatocyte-specific FOXA2 knockout mice. Adeno-associated virus AAV8-TBG-Control or AAV8-TBG-Cre was injected via the tail vein of FOXA2flox/flox (FOXA2f/f) mice 2 weeks prior to CCl4 administration. Hepatic fibrosis was induced by injection of CCl4 twice per week for 4 weeks.
2017-04-04 | GSE97344 | GEO