Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66750 | GEO | 2016/01/04

SECONDARY ACCESSION(S): PRJNA277859

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

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

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

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

2015-12-11 | GSE66956 | GEO

Epigenetic regulation of hematopoiesis by DNA methylation

Project description:Purpose: RNA seq analysis from isolated zebrafish HSPCs at 48 hpf from control morpholino and dnmt3bb.1 morpholino injected embryos

2017-02-09 | GSE74929 | GEO

Transcriptional profiling of embryonic zebrafish expressing a mutant TNNT2

Project description:Transcriptional profiling of embryonic zebrafish injected with a control morpholino or a morpholino that causes exclusion of TNNT2 exon 13.

2010-12-31 | GSE20179 | GEO

Transcriptional profiling of embryonic zebrafish expressing a mutant TNNT2

Project description:Transcriptional profiling of embryonic zebrafish injected with a control morpholino or a morpholino that causes exclusion of TNNT2 exon 13. Zebrafish embryos were injected with a antisense morpholino oligo that induced missplicing of exon 13 of TNNT2 (TNNT2sp) or a control morpholino. At 96hpf these embryos were euthanized and RNA was collected.

2010-12-31 | E-GEOD-20179 | biostudies-arrayexpress

RNA-seq of the anterior third (head) region of fifty pooled danio rerio embryos at the 15-somite stage following crispld2 morpholino knockdown compared to uninjected controls

Project description:We have a well characterized crispld2 morpholino in the danio rerio organism system. The aim of this experiment was to determine differential gene expression in the morpholino zebrafish compared to uninjected zebrafish.

2018-05-13 | E-MTAB-6705 | biostudies-arrayexpress

Zebrafish embryos: hdac1 Morphants vs Standard control morphants

Project description:Transcriptional profiling of hdac1 morphant zebrafish embryos in comparison to standard control injected embryos. Embryos where injected at the one cell stage with either a translation blocking morpholino (Hdac1 ATG), splice blocking morpholino (Hdac1 Splice) or Hdac1 mismatch control morpholino (Hdac1 control). RNA was extracted and compared in a two-colour hybridisation to the comman reference Standard control morpholino injected embryos.

2011-01-21 | GSE26708 | GEO

The effect of cardiac troponin T2 knockdown on gene expression in zebrafish embryos

Project description:We examined the transcriptional effect of preventing cardiac contraction in zebrafish embryos which can be deprived of circulation without experiencing hypoxia since the fish obtain sufficient oxygen via diffusion. Morpholino antisense knockdown of cardiac troponin T2 (tnnt2) prevented cardiac contraction without affecting vascular development. We concluded that absence of hemodynamic force induces endothelial CXCR4a up-regulation and promotes recovery of blood flow. We used microarrays to define the genetic signatures of the development of collateral vessels in zebrafish. Keywords: Time course comparison of wild type zebrafish embryos and morpholino antisense against troponin t2 treated embryos.

2009-06-24 | GSE16740 | GEO

RNA-seq of HNRNPAB morpholino in zebrafish

Project description:RNA-seq of HNRNPAB morpholino in zebrafish

| PRJNA820769 | ENA