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| Status |
Public on Aug 11, 2011 |
| Title |
Genetic Framework for GATA Factor Function in Vascular Biology |
| Project |
ENCODE
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| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Vascular endothelial dysfunction underlies the genesis and progression of numerous diseases. Whereas the GATA transcription factor GATA-2 is expressed in endothelial cells and is implicated in coronary heart disease, it has been studied predominantly as a master regulator of hematopoiesis. As many questions remain unanswered regarding GATA-2 function in the vascular biology realm, we used ChIP-seq and loss-of-function strategies to define the GATA-2-instigated genetic network in human endothelial cells. By contrast to erythroid cells, GATA-2 occupied a unique target gene ensemble, consisting of genes encoding key determinants of endothelial cell identity and inflammation. GATA-2-occupied sites characteristically contained motifs that bind Activator Protein-1 (AP-1), a pivotal regulator of inflammatory genes. GATA-2 frequently occupied the same chromatin sites as c-JUN and c-FOS, heterodimeric components of AP-1. Though all three components were required for maximal AP-1 target gene expression, GATA-2 was not required for AP-1 chromatin occupancy. GATA-2 conferred maximal phosphorylation of chromatin-bound c-JUN at Ser 73, which stimulates AP-1-dependent transactivation, in a chromosomal context-dependent manner. This work establishes a link between a GATA factor and inflammation, mechanistic insights underlying GATA-2-AP-1 cooperativity, and a rigorous genetic framework for understanding GATA-2 function in normal and pathophysiological vascular states.
For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf
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| Overall design |
Examination of GATA2 ChIP-seq in HUVEC cells.
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| Web link |
http://www.ncbi.nlm.nih.gov/geo/info/ENCODE.html
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| Contributor(s) |
Linnemann AK, O'Geen H, Keles S, Farnham PJ, Bresnick EH |
| Citation(s) |
21808000 |
| BioProject |
PRJNA63447 |
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| Submission date |
May 25, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Philip Cayting |
| E-mail(s) |
pcayting@stanford.edu
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| Organization name |
Stanford University
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| Department |
Genetics
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| Lab |
Snyder
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| Street address |
1501 S California Ave
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| City |
Palo Alto |
| State/province |
CA |
| ZIP/Postal code |
94304 |
| Country |
USA |
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| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
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| Samples (5)
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| Relations |
| SRA |
SRP006967 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE29531_RAW.tar |
2.6 Gb |
(http)(custom) |
TAR (of BAM) |
| GSE29531_wgEncodeSydhTfbsHuvecCfosUcdPk.narrowPeak.gz |
944.7 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE29531_wgEncodeSydhTfbsHuvecCfosUcdSig.bigWig |
344.8 Mb |
(ftp)(http) |
BIGWIG |
| GSE29531_wgEncodeSydhTfbsHuvecGata2UcdPk.narrowPeak.gz |
591.4 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE29531_wgEncodeSydhTfbsHuvecGata2UcdSig.bigWig |
369.6 Mb |
(ftp)(http) |
BIGWIG |
| GSE29531_wgEncodeSydhTfbsHuvecInputUcdSig.bigWig |
351.0 Mb |
(ftp)(http) |
BIGWIG |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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