Functional characteristics of novel pancreatic Pax6 regulatory using a mouse pancreatic cell model
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ABSTRACT:
PROVIDER: PRJNA480282 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7500608.fastq.gz | Fastqsanger.gz | |||
| SRR7500609.fastq.gz | Fastqsanger.gz |
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Project description:Transcriptome profiling using RNA-seq of β-TC3 cell, a mouse pancreatic cell line used in the study of novel Cis-regulatory elements for the Pax6 gene .
2018-08-01 | GSE116811 | GEO
Project description:Complex diseases, such as diabetes, are influenced by comprehensive transcriptional networks. Genome-wide association studies have revealed that variants located in regulatory elements for pancreatic transcription factors are linked to diabetes, including those functionally linked to the paired box transcription factor Pax6. Pax6 deletions in adult mice cause rapid onset of classic diabetes, but the full spectrum of pancreatic Pax6 regulators is unknown. Using a regulatory element discovery approach, we identified two novel Pax6 pancreatic cis-regulatory elements in a poorly characterized regulatory desert. Both new elements, Pax6 pancreas cis-regulatory element 3 (PE3) and PE4, are located 50 and 100 kb upstream and interact with different parts of the Pax6 promoter and nearby non-coding RNAs. They drive expression in the developing pancreas and brain and code for multiple pancreas-related transcription factor-binding sites. PE3 binds CCCTC-binding factor (CTCF) and is marked by stem cell identity markers in embryonic stem cells, whilst a common variant located in the PE4 element affects binding of Pax4, a known pancreatic regulator, altering Pax6 gene expression. To determine the ability of these elements to regulate gene expression, synthetic transcriptional activators and repressors were targeted to PE3 and PE4, modulating Pax6 gene expression, as well as influencing neighbouring genes and long non-coding RNAs, implicating the Pax6 locus in pancreas function and diabetes.
| S-EPMC6140780 | biostudies-literature
Project description:The transcription factor Pax6 is comprised of the paired domain (PD) and homeodomain (HD). In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific subpopulations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification. Pax6 also regulates the entire lens developmental program. To reconstruct Pax6-dependent gene regulatory networks (GRNs), ChIP-seq studies were performed using lens and forebrain chromatin from mice. A total of 3,723 (forebrain) and 3,514 (lens) Pax6-containing peaks were identified, with ~70% of them found in both tissues and thereafter called “common” peaks. Analysis of Pax6-bound peaks identified motifs that closely resemble Pax6-PD, -PD/HD and -HD established binding sequences. Mapping of H3K4me1, H3K4me3, H3K27ac, H3K27me3 and RNA polymerase II revealed distinct types of tissue-specific enhancers bound by Pax6. Pax6 directly regulates cortical neurogenesis through activation (e.g. Dmrta1 and Ngn2) and repression (e.g. Ascl1, Fezf2, and Gsx2) of transcription factors. In lens, Pax6 directly regulates cell cycle exit control via components of FGF (Fgfr2, Ccnd1, and Prox1) and Wnt (Dkk3, Wnt7a, Lrp6, Bcl9l, and Ccnd1) signaling pathways. Collectively, these studies provide genome-wide analysis of Pax6-dependent GRNs in lens and forebrain and establish novel roles of Pax6 in organogenesis. Examination of Pax6 in mouse embryonic forebrain and newborn lens. We performed ChIP-seq on mouse E12.5 embryonic forebrain and newborn lens. Genome-wide binding sites of Pax6, H3K4me1, H3K4me3, H3K27ac, H3K27me3, and Pol2 were generated. We also performed RNA-seq on mouse E12.5 embryonic forebrain and newborn lens epithelial cells and fibers.
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Project description:Gut microbial characteristics in pancreatic carcinoma patients
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Project description:The transcription factor Pax6 is comprised of the paired domain (PD) and homeodomain (HD). In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific subpopulations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification. Pax6 also regulates the entire lens developmental program. To reconstruct Pax6-dependent gene regulatory networks (GRNs), ChIP-seq studies were performed using lens and forebrain chromatin from mice. A total of 3,723 (forebrain) and 3,514 (lens) Pax6-containing peaks were identified, with ~70% of them found in both tissues and thereafter called “common” peaks. Analysis of Pax6-bound peaks identified motifs that closely resemble Pax6-PD, -PD/HD and -HD established binding sequences. Mapping of H3K4me1, H3K4me3, H3K27ac, H3K27me3 and RNA polymerase II revealed distinct types of tissue-specific enhancers bound by Pax6. Pax6 directly regulates cortical neurogenesis through activation (e.g. Dmrta1 and Ngn2) and repression (e.g. Ascl1, Fezf2, and Gsx2) of transcription factors. In lens, Pax6 directly regulates cell cycle exit control via components of FGF (Fgfr2, Ccnd1, and Prox1) and Wnt (Dkk3, Wnt7a, Lrp6, Bcl9l, and Ccnd1) signaling pathways. Collectively, these studies provide genome-wide analysis of Pax6-dependent GRNs in lens and forebrain and establish novel roles of Pax6 in organogenesis.
2015-07-09 | GSE66961 | GEO
Project description:This is an integrative genome-wide approach to identify downstream networks controlled by Pax6 during mouse lens and forebrain development. Differential gene expression was analyzed in Pax6 mouse heterozygous and wildtype newborn mouse lenses, with subsequent comparison of this data with Pax6 forebrain expression data (Holm et al., 2007). Keywords: Differential gene expression
2008-10-17 | GSE13244 | GEO
Project description:During organogenesis, PAX6 is required for establishment of various progenitor subtypes within the central nervous system, eye and pancreas. PAX6 expression is maintained in a variety of cell types within each organ, although its role in each lineage and how it acquires cell-specific activity remain elusive. Herein, we aimed to determine the roles and the hierarchical organization of the PAX6-dependent gene regulatory network during the differentiation of the retinal pigmented epithelium (RPE). Somatic mutagenesis of Pax6 in the differentiating RPE revealed that PAX6 functions in a feed-forward regulatory loop with MITF during onset of melanogenesis. PAX6 both controls the expression of an RPE isoform of Mitf and synergizes with MITF to activate expression of genes involved in pigment biogenesis. This study exemplifies how one kernel gene pivotal in organ formation accomplishes a lineage-specific role during terminal differentiation of a single lineage. The data contains 3 control and 3 Pax6 negative samples representing biological repeats. Each sample was prepared from RPE dissected from E15.5 transgenic animals, either Pax6loxP/loxP or Pax6loxP/loxP;DctCre.
2014-04-08 | E-GEOD-56548 | biostudies-arrayexpress
Project description:Pancreatic cancer is a dangerous malignancy in the pancreas. In this study we use single-cell RNA sequencing technique to help understand the transcriptome characteristics of pancreatic tumor cells. This study help understands the complex microenvironment of pancreatic tumors and will likely to benefit clinical research of pancreatic cancer treatments.
| EGAS00001003889 | EGA
Project description:The transcription factor Pax6 acts as a key developmental regulator in various organs. In the developing brain Pax6 regulates patterning, neurogenesis and proliferation, but how these diverse effects are mediated at the molecular level is not well understood. As Pax6 regulates forebrain development including neurogenesis, proliferation and patterning, almost exclusively by one of its DNA-binding domains, the bipartite paired domain, we examined the role of its respective DNA-binding subdomains (PAI and RED). Using mice with point mutations in the PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C) subdomains we unravelled opposing roles of mutations in these subdomains in regulating genes that control proliferation in the developing cerebral cortex. Mutation of the PAI domain reduced proliferation of both apical and basal progenitors, while the RED domain mutation significantly increased proliferation. Conversely, neurogenesis was affected only by the PAI domain mutation phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression analysis supported the molecularly distinct signature upon mutation of these subdomains unravelling the key neurogenic signature mediated by the PAI domain. The altered expression of genes identified as direct Pax6 targets by chromatin immunoprecipitation allowed to further identify regulatory elements whose function was impaired by each individual Pax6 mutated protein. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing distinct subdomains to regulate neurogenesis and exert opposing effects on proliferation, while Pax6-target genes involved in patterning tolerate either subdomain mutation. We performed gene expression microarray analysis of Pax6 mutant mice (Leca2, Leca4, Sey) and control mice
2013-03-19 | E-GEOD-35260 | biostudies-arrayexpress