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| Status |
Public on Dec 11, 2015 |
| Title |
Genome-wide analysis reveals NRP1 as a critical HIF1-E2F7 target gene in the regulation of motorneuron guidance in vivo |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
ChIP-seq analysis of HIF1a and E2F7 binding
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| Contributor(s) |
de Bruin A, Cornelissen P, Kirchmaier B, Mokry M, Iich E, Nirmala E, Liang K, Végh A, Scholman K, Groot Koerkamp M, Holstege F, Cuppen E, den Hertog J, Schulte-Merker S, Bakker W |
| Citation(s) |
26681691 |
| Submission date |
Mar 16, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Michal Mokry |
| E-mail(s) |
m.mokry@umcutrecht.nl
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| Organization name |
Wilhelmina Children's Hospital, University Medical Center Utrecht
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| Street address |
Lundlaan 6
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| City |
Utrecht |
| ZIP/Postal code |
3584 EA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL13393 |
AB SOLiD 4 System (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA278464 |
| SRA |
SRP056218 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66956_RAW.tar |
560.0 Kb |
(http)(custom) |
TAR (of COD) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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