Detection of non-coding deletion CNVs upstream to FOXF1 [Agilent-022084]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Erwin Brosens
PROVIDER: E-GEOD-38978 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Genomic copy number analysis in patients with ACD/MPV. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development.potentially cause many disorders of human development. CNVs were identified by array CGH with custom-designed 16q24.1 region specific (1Mb flanking FOXF1) 44K oligonucleotide microarrays (Agilent technologies) in 3 patients with ACD.
2012-07-10 | E-GEOD-39254 | biostudies-arrayexpress
Project description:Genomic copy number analysis in patients with ACD/MPV. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development.potentially cause many disorders of human development.
2012-07-11 | GSE39254 | GEO
Project description:Chromatin immunoprecipitation with anti-GLI2 antibody was conducted in human pulomonary microvascular endothelial cells (HPMECs) to determine GLI2 binding sites upstream of FOXF1. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development. ChIP-chip HPMECs transfected to overxpress GLI2; 2 biological replicates
2012-07-10 | E-GEOD-39255 | biostudies-arrayexpress
Project description:Genomic copy number analysis in patients with ACD/MPV. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development.potentially cause many disorders of human development. CNVs were identified by array CGH with custom-designed 16q24.1 region specific (1Mb flanking FOXF1) 44K oligonucleotide microarrays (Agilent technologies) in 3 patients with ACD. This Series contains data for only two patients
2012-07-06 | GSE38978 | GEO
Project description:To determine if there is a physical interaction between the FOXF1 promoter and putative enhancer sequences ~250kb upstream of the promoter chromosome conformation capture-on-chip (4C) analysis was performed. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development. 4C analysis using 16q24.1 specific 3x720K arrays demonstrated physical interaction between the FOXF1 promoter and distant putative regulatory sequences, about 250 kb upstream in human pulomonary microvascular endothelial cells; 2 biological replicates performed; this chromatin looping was not detected in lymphoblasts that do not express FOXF1 and hence serve as a negative control.
2012-07-10 | E-GEOD-39256 | biostudies-arrayexpress
Project description:Non-coding copy number changes in 16q24.1 upstream of FOXF1 were identified in two patients with ACD. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development.
2012-07-11 | GSE39257 | GEO
Project description:To determine if there is a physical interaction between the FOXF1 promoter and putative enhancer sequences ~250kb upstream of the promoter chromosome conformation capture-on-chip (4C) analysis was performed. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development.
2012-07-11 | GSE39256 | GEO
Project description:Chromatin immunoprecipitation with anti-GLI2 antibody was conducted in human pulomonary microvascular endothelial cells (HPMECs) to determine GLI2 binding sites upstream of FOXF1. An unanticipated and tremendous amount of the non-coding sequences of the human genome are transcribed. Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides and their functions remain enigmatic. We demonstrate that deletions of lncRNA genes cause a lethal lung developmental disorder, Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV), with parent of origin effects. We identify non-coding overlapping deletions 250 kb upstream to FOXF1 in nine patients with ACD/MPV that arose de novo specifically on the maternally inherited chromosome and delete a fetal lung-specific EST, part of an lncRNA. These deletions define distant cis-regulatory region that harbors a differentially methylated CpG island, binds GLI2 depending on the methylation status of this CpG island, and physically interacts with and up-regulates the FOXF1 promoter, consistent with the absence of the fetal lung-transcribed lncRNA perturbing FOXF1 regulation. LncRNA-mediated chromatin interactions may be responsible for position effect phenomenon and potentially cause many disorders of human development.
2012-07-11 | GSE39255 | GEO
Project description:Aberrant expression of master phenotype regulators by lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus, we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF compared with controls. In normal lung fibroblasts, FOXF1 repressed key fibroblast functions such as proliferation, survival, and expression of collagen-1 (COL1) and actin related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown mimicked FOXF1 overexpression with regard to proliferation and COL1 expression. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E2 (PGE2). Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant and survive in uninjured mouse lungs. In IPF lung fibroblasts, FOXF1 regulated COL1 but not ARPC2 expression. In conclusion, FOXF1 functions and regulation were consistent with an antifibrotic role in lung fibroblasts. Higher FOXF1 levels in IPF fibroblasts may thus participate in a compensatory response to fibrogenesis. Lung fibroblasts derived from 4 different IPF patients (P313, P355, P375 and P426) were transiently transfected with pcfoxf1 or control pcDNA3.1-constructs. Total RNAs were extracted 24 h after transfection and hybridized on microarrays. One color experiment with 2 experimental conditions: pcfoxf1 and pcDNA3.1
2014-10-01 | E-GEOD-52612 | biostudies-arrayexpress
Project description:Multiple signaling pathways, structural proteins and transcription factors are involved in regulation of endothelial barrier function. The Forkhead protein FOXF1 is a key transcriptional regulator of lung embryonic development, and we use a conditional knockout approach to examine the role of FOXF1 in adult lung homeostasis and lung injury and repair. Tamoxifen-regulated deletion of both Foxf1 alleles in endothelial cells of adult mice (Pdgfb-iCreER/Foxf1 caused lung inflammation and edema, leading to respiratory insuffency and uniform mortality. Deletion of a single foxf1 allele was sufficient to increase susceptibility of heterozygous mice to acute lung injury. FOXF1 abundance was decreased in pulmonary endothelial cells of human patients with acute lung injury. Gene expression analysis of pulmonary endothelial cells of FOXF1 deletion indicated reduced expression for genes critical for maintance and regulation of adherens junctions. FOXF1 knockdown in vitro and in vivo disrupted adherens junctions, increased lung endothelial permeability, and the abundance of mRNA and protein for sphingosine 1 phosphate receptor 1 (S1PR1), a key regulator of endothelial barrier function. Chromatin immunoprecipitation and luciferase reporter assay demonstrated that FOXF1 directly bound to and induced the tanscriptional activity of the S1pr1 promoter. Pharmacological administratiion of S1P to injured pdgfb-iCreER/Foxf1 mice restored endothelial barrier function, decreased lung edema and improved survival. Thus, FOXF1 promotes normal lung homeostasis and lung repair, at least in part, by enhancing endothelial barrier function through transcriptional activation of the S1P/S1PR1/ signaling pathway.
2016-04-20 | GSE78184 | GEO