Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide analysis reveals NRP1 as a critical HIF1-E2F7 target gene in the regulation of motorneuron guidance in vivo

ABSTRACT: HIF1 is essential for regulation of the transcriptional response to hypoxia. Recently we showed that the transcriptional repressors E2F7 and E2F8 interact and transcriptionally cooperate with HIF1. Here we further explored this cooperation by performing genome-wide analysis, screening for novel HIF1-E2F7 targets. We show that specifically E2F7 is induced in hypoxia by HIF1. Furthermore, chip-sequencing for E2F7 and HIF1 revealed a large number of common targets of which a subset was also regulated by the complex as examined by microarray analysis. Our data show that the HIF1-E2F7 complex can function both as a repressor or activator. Notably, we identify neuropilin 1 (NRP1) as a novel HIF1-E2F7 target, which is repressed by HIF1-E2F7 in vitro and during zebrafish development, depending on E2F-binding sites present in the NRP1 promoter. In addition we show that regulation of NRP1 by the HIF1-E2F7 complex is required for normal axon guidance of spinal motorneurons in vivo.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66956 | GEO | 2015/12/11

SECONDARY ACCESSION(S): PRJNA278464

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide analysis reveals NRP1 as a critical HIF1-E2F7 target gene in the regulation of motorneuron guidance in vivo

Project description:HIF1 is essential for regulation of the transcriptional response to hypoxia. Recently we showed that the transcriptional repressors E2F7 and E2F8 interact and transcriptionally cooperate with HIF1. Here we further explored this cooperation by performing genome-wide analysis, screening for novel HIF1-E2F7 targets. We show that specifically E2F7 is induced in hypoxia by HIF1. Furthermore, chip-sequencing for E2F7 and HIF1 revealed a large number of common targets of which a subset was also regulated by the complex as examined by microarray analysis. Our data show that the HIF1-E2F7 complex can function both as a repressor or activator. Notably, we identify neuropilin 1 (NRP1) as a novel HIF1-E2F7 target, which is repressed by HIF1-E2F7 in vitro and during zebrafish development, depending on E2F-binding sites present in the NRP1 promoter. In addition we show that regulation of NRP1 by the HIF1-E2F7 complex is required for normal axon guidance of spinal motorneurons in vivo. ChIP-seq analysis of HIF1a and E2F7 binding

2015-12-11 | E-GEOD-66956 | biostudies-arrayexpress

WB001A: Genome-wide analysis reveals NRP1 as a critical HIF1-E2F7 target gene in the regulation of motor neuron guidance in vivo

Project description:In this study, we explored the existence of a transcriptional network co-regulated by E2F7 and HIF1Î±, as we show that expression of E2F7, like HIF1Î±, is induced in hypoxia, and because of the previously reported ability of E2F7 to interact with HIF1Î±. Our genome-wide analysis uncovers a transcriptional network that is directly controlled by HIF1Î± and E2F7, and demonstrates both stimulatory and repressive functions of the HIF1Î± -E2F7 complex. Among this network we reveal Neuropilin 1 (NRP1) as a HIF1Î±-E2F7 repressed gene. By performing in vitro and in vivo reporter assays we demonstrate that the HIF1Î±-E2F7 mediated NRP1 repression depends on a 41 base pairs 'E2F-binding site hub', providing a molecular mechanism for a previously unanticipated role for HIF1Î± in transcriptional repression. To explore the biological significance of this regulation we performed in situ hybridizations and observed enhanced nrp1a expression in spinal motorneurons (MN) of zebrafish embryos, upon morpholino-inhibition of e2f7/8 or hif1Î±. Consistent with the chemo-repellent role of nrp1a, morpholino-inhibition of e2f7/8 or hif1Î± caused MN truncations, which was rescued in TALEN-induced nrp1a(hu10012) mutants, and phenocopied in e2f7/8 mutant zebrafish. Therefore, we conclude that repression of NRP1 by the HIF1Î±-E2F7 complex regulates MN axon guidance in vivo. The following samples were analyzed by microarrays: RNA isolated from HeLa cells transfected with either control (scr), E2F7, HIF1a, E2F7 and E2F8, or E2F7 and HIF1a siRNAs. Cells were harvested 48h after transfection, and were grown the last 16h in hypoxia. RNA isolated from scr-transfected, normoxic HeLa cells was used as common reference RNA. Within each group of two biological replicates, sample versus common reference hybridisations were performed in balanced dye-swap. Microarrays used were human whole genome gene expression microarrays V1 (Agilent, Belgium).

2016-01-04 | E-GEOD-66750 | biostudies-arrayexpress

WB001A: Genome-wide analysis reveals NRP1 as a critical HIF1-E2F7 target gene in the regulation of motor neuron guidance in vivo

Project description:In this study, we explored the existence of a transcriptional network co-regulated by E2F7 and HIF1α, as we show that expression of E2F7, like HIF1α, is induced in hypoxia, and because of the previously reported ability of E2F7 to interact with HIF1α. Our genome-wide analysis uncovers a transcriptional network that is directly controlled by HIF1α and E2F7, and demonstrates both stimulatory and repressive functions of the HIF1α -E2F7 complex. Among this network we reveal Neuropilin 1 (NRP1) as a HIF1α-E2F7 repressed gene. By performing in vitro and in vivo reporter assays we demonstrate that the HIF1α-E2F7 mediated NRP1 repression depends on a 41 base pairs 'E2F-binding site hub', providing a molecular mechanism for a previously unanticipated role for HIF1α in transcriptional repression. To explore the biological significance of this regulation we performed in situ hybridizations and observed enhanced nrp1a expression in spinal motorneurons (MN) of zebrafish embryos, upon morpholino-inhibition of e2f7/8 or hif1α. Consistent with the chemo-repellent role of nrp1a, morpholino-inhibition of e2f7/8 or hif1α caused MN truncations, which was rescued in TALEN-induced nrp1a(hu10012) mutants, and phenocopied in e2f7/8 mutant zebrafish. Therefore, we conclude that repression of NRP1 by the HIF1α-E2F7 complex regulates MN axon guidance in vivo.

2016-01-04 | GSE66750 | GEO

E2f7/E2f8 and E2f1/E2f2/E2f3 null and wild type liver along with E2f7/E2f8 null and wild type trophoblast giant cells

Project description:This SuperSeries is composed of the following subset Series: GSE32353: Expression data from E2f7/E2f8 and E2f1/E2f2/E2f3 null and wild type liver along with E2f7/E2f8 null and wild type trophoblast giant cells (nCounter) GSE32354: Expression data from E2f7/E2f8 and E2f1/E2f2/E2f3 null liver (Affymetrix) Refer to individual Series

2012-08-31 | E-GEOD-32355 | biostudies-arrayexpress

Expression data from E2f7/E2f8/E2f3a null placentas and embryos

2012-08-31 | GSE30488 | GEO

Expression data from E2f7/E2f8/E2f3a null placentas and embryos

Project description:To understand the underlying cause and mechanisms of embryonic lethality observed in combined loss of E2f7 and E2f8, we compared global gene expression profiles of wild type, germline deleted and sox2-Cre/Cyp19-Cre deleted embryos and placentas. RNA was extracted from E10.5 embryos and placentas. Gene deletion in samples confirmed by PCR genotyping of DNA isolated from each sample.

2012-08-31 | E-GEOD-30488 | biostudies-arrayexpress

LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1⍺ Activity [ChIP-seq]

Project description:Glioblastoma (GBM) is characterized by a high degree of hypoxia. Hypoxia-inducible factors (HIFs) modulate glioma stem-like cell (GSC) responses to hypoxia and promote GBM progression, therapeutic resistance, and recurrence. Here we identify a new transcript of the long non-coding RNA LUCAT1 and show that it reinforces HIF1⍺ signaling in GSCs under hypoxia. LUCAT1 expression is highly induced under hypoxia in GBM and GSCs in a HIF1⍺-dependent manner. High LUCAT1 expression in human GBM correlates with increased aggression and poor survival. Mechanistically, LUCAT1 associates with chromatin and modulates interaction between HIF1⍺ and coactivator CBP to hypoxia response elements (HREs) to drive HIF1⍺-target gene expression under hypoxia. Thus, LUCAT1 acts as a positive feedback factor to augment HIF1⍺ signaling under hypoxic stress in GSCs. Loss of LUCAT1 reduces tumor growth and prolongs mouse survival in xenograft models of GBM. Our findings provide new insights into how GSCs regulate gene expression under hypoxia and identify LUCAT1 as therapeutic target in GBM.

2024-03-12 | GSE255502 | GEO

LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1⍺ Activity [RNA-seq]

2024-03-12 | GSE255501 | GEO

Identification of HIF1 and HIF2 target genes in human CB CD34+ cells

Project description:Although it has been shown that HIF1 and 2 fulfill essential roles within the hematopoietic system and in the regulation of HSC fate, little is currently known about the specific mechanisms that are involved. We identified transcriptome changes induced by hypoxia, constitutively active HIF1(P402/564) and HIF2(P405/531) in human cord blood CD34+ cells. Thus, we were able to identify common hypoxia-HIF1-HIF2 gene signatures, but we also identified specific target genes that were exclusively regulated by HIF1, HIF2 or hypoxia.

2014-03-01 | GSE54662 | GEO

Genome-wide binding sites of Hypoxia inducible factor 1 (HIF1) and histone modifications

Project description:We report the high-throughput profilings of HIF1 and histone modifications in human umbilical vein endothelial cells (HUVEC). By obtaining over two billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of HUVEC under normoxia and hypoxia. We find that HIF1binds to not only to transcriptional starting sites but also enhancer regions and that HIF1 binding sites were overlapped with lysine 4 trimethylatio, monomethylation and lysine 27 acetylation . Finally, we show that chromatin state can change under hypoxia by using chromatin conformational capture assay. This study provides novel insights into the interaction between HIF1 and KDM3A and also the epigenetic regulation of HIF1. Examination of HIF1 and 3 different histone modifications in HUVEC under 2 conditions. Related gene expression data is provided in GSE35932.

2012-07-12 | E-GEOD-39089 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data