Global analysis of NFATc1 targets in human vascular endothelial cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE49426 | GEO | 2013/09/01
SECONDARY ACCESSION(S): PRJNA213893
REPOSITORIES: GEO
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Project description:We performed the newly mapping of genome-wide NFATc1 binding events in VEGF-stimulated primary cultured endothelial cells, by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Combined NFATc1 ChIP-seq profile and the epigenetic histone marks revealed that predominant NFATc1-occupied peaks were overlapped with promoter marking but not silencer marking. DNA microarrays with NFATc1 expression or knockdown indicated the predominant NFATc1 binding targets were correlated with induced patterns. Examination of NFATc1 and two different histone marks in HUVEC in the presence/absense of VEGF.
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Project description:We performed the newly mapping of genome-wide NFATc1 binding events in VEGF-stimulated primary cultured endothelial cells, by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Combined NFATc1 ChIP-seq profile and the epigenetic histone marks revealed that predominant NFATc1-occupied peaks were overlapped with promoter marking but not silencer marking. DNA microarrays with NFATc1 expression or knockdown indicated the predominant NFATc1 binding targets were correlated with induced patterns. To determine NFATc1-regulated genes, a total of 5 samples were derived from human umbilical vein endothelial cells (HUVECs) stimulated with or without 50ng/mL VEGF (VEGF 60min and 0min, respectively), pretreated with cyclosporine A (VEGF 60min plus CsA) and infected with adenovirus expressing the control or constitutively active NFATc1 (Ad-control and Ad-NFATc1).
2013-09-01 | E-GEOD-49426 | biostudies-arrayexpress
Project description:We performed the newly mapping of genome-wide NFATc1 binding events in VEGF-stimulated primary cultured endothelial cells, by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Combined NFATc1 ChIP-seq profile and the epigenetic histone marks revealed that predominant NFATc1-occupied peaks were overlapped with promoter marking but not silencer marking. DNA microarrays with NFATc1 expression or knockdown indicated the predominant NFATc1 binding targets were correlated with induced patterns.
2013-09-01 | GSE49428 | GEO
Project description:Inflammatory transcription networks have been linked with the development of pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrate that NFATc1 is both necessary and sufficient to drive progression of KrasG12D-initiated PDAC, particularly in the context of inflammation. Significantly, nuclear NFATc1 accelerates PDAC development in KrasG12D mice, whereas conditional NFATc1 deletion or pharmacological inhibition attenuates inflammation-mediated carcinogenesis. Mechanistically, NFATc1 induces STAT3 expression, complex formation and signal integration in PDAC. Genome-wide ChIP-sequencing and expression analysis in cells derived from c.n.NFATc1;KrasG12D mice identified combinatorial NFATc1/STAT3 binding at chromatin enhancer sites and subsequent regulation of key molecules involved in oncogenic signaling, growth and inflammation. Together, this study supports the relevance of inflammatory transcription factor networks in pancreatic carcinogenesis and provides a theoretical platform for therapeutic targeting of NFATc1 nucleoprotein complexes in PDAC. NFATc1 ChIP followed by high throughput sequencing in primary murine pancreatic cancer cells (referred to as NKC cells) derived from transgenic mice with pancreas-specific constitutive activation of NFATc1 and KrasG12D mutation in the presence or absence of STAT3 shRNA; 2 ChIP samples (scramble DNA and shSTAT3 DNA) and 1 unenriched input control from the same chromatin pool.
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Project description:Inflammatory transcription networks have been linked with the development of pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrate that NFATc1 is both necessary and sufficient to drive progression of KrasG12D-initiated PDAC, particularly in the context of inflammation. Significantly, nuclear NFATc1 accelerates PDAC development in KrasG12D mice, whereas conditional NFATc1 deletion or pharmacological inhibition attenuates inflammation-mediated carcinogenesis. Mechanistically, NFATc1 induces STAT3 expression, complex formation and signal integration in PDAC. Genome-wide ChIP-sequencing and expression analysis in cells derived from c.n.NFATc1;KrasG12D mice identified combinatorial NFATc1/STAT3 binding at chromatin enhancer sites and subsequent regulation of key molecules involved in oncogenic signaling, growth and inflammation. Together, this study supports the relevance of inflammatory transcription factor networks in pancreatic carcinogenesis and provides a theoretical platform for therapeutic targeting of NFATc1 nucleoprotein complexes in PDAC.
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Project description:In lymphocytes, NFATc1 is the most prominent NFAT transcription factor which play a crucial role in the fate and activity of peripheral T and B cells. NFATc1 is synthesized in two prominent isoforms, the inducible short isoform NFATc1/aA and the constitutively expressed long isoform NFATc1/C. Several lines of evidence suggested that both isoforms differ markedly in their function. It was speculated that NFATc1/aA supports the proliferation and survival of lymphocytes, whereas NFATc1/C should support apoptosis and anergy induction. To proof this hypothesis we established WEHI 231 B lymphoma cells that stably (over-) express either NFATc1/aA or NFATc1/C. In preliminary experiments we could should that WEHI cells overexpressing NFATc1/aA were protected against apoptosis induction, while cells overexpressing NFATc1/C should a higher apoptosis rate. Transcriptom analysis of WEHI-231 cells overexpressing either NFATc1/aA or NFATc1/C were performed, along with a control group of WEHI-231 cells overexpressing the E.coli enzyme BirA Ligase (which is also present in all target cell lines since for further molecular assays the NFATc1 proteins were expressed as chimeric protein containing C-terminal bio-tags. The experimental results obtained indicate that the both NFATc1 proteins, NFATc1/aA and NFATc1/C, differ tremendously in their transcriptional properties.
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2014-05-06 | E-GEOD-57314 | biostudies-arrayexpress
Project description:We find that epithelial-specific deletion of Nfatc1 decreases skin tumor susceptibility in mice subjected to DMBA/TPA carcinogenesis. To probe the molecular mechanisms by which Nfatc1 may regulate tumorigenesis, we identify gene expression changes associated with constitutive NFATc1 activation in primary mouse keratinocytes. Constitutively active NFATc1 activity in primary mouse keratinocytes to investigate how Nfatc1 regulates tumor initiation in the skin.
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