PXD008581 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNAAngiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA |
Description | Endothelial cell (EC)-enriched protein coding genes, such as endothelial nitric oxide synthase (eNOS), define quintessential EC-specific physiologic functions. It is not clear whether long noncoding RNAs (lncRNAs) also define cardiovascular cell-type specific phenotypes, especially in the vascular endothelium. Here, we report the existence of a set of EC-enriched lncRNAs and define a role for STEEL (spliced transcript – endothelial enriched lncRNA) in angiogenic potential, macrovascular/microvascular identity and shear stress responsiveness. STEEL is expressed from the terminus of the HOXD locus and is transcribed antisense to HOXD transcription factors. STEEL RNA increases the number and integrity of de novo perfused microvessels in an in vivo model and augments angiogenesis in vitro. The STEEL RNA is polyadenylated, nuclear-enriched and has microvascular predominance. Functionally, STEEL regulates a number of genes in diverse endothelial cells. Of interest, STEEL upregulates both eNOS and the transcription factor Kruppel-like factor 2 (KLF2), and is subject to feedback inhibition by both eNOS and shear-augmented KLF2. Mechanistically, STEEL upregulation of eNOS and KLF2 is transcriptionally mediated, in part, via interaction of chromatin-associated STEEL with the poly-ADP ribosylase, PARP1. For instance, STEEL recruits PARP1 to the KLF2 promoter. This work identifies a role for EC-enriched lncRNAs in the phenotypic adaptation of ECs to both body position and hemodynamic forces, and establishes a newer role for lncRNAs in the transcriptional regulation of EC identity. |
HostingRepository | PRIDE |
AnnounceDate | 2019-03-06 |
AnnouncementXML | Submission_2019-03-06_02:11:45.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD008581 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Jonathan Krieger |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | Phospho; Deamidated; Oxidation; Carbamidomethyl |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-01-02 07:20:08 | ID requested | |
1 | 2018-02-28 05:59:58 | announced | |
2 | 2018-03-01 00:30:23 | announced | Updated project metadata. |
⏵ 3 | 2019-03-06 02:11:46 | announced | Updated project metadata. |
Publication List
Man HSJ, Sukumar AN, Lam GC, Turgeon PJ, Yan MS, Ku KH, Dubinsky MK, Ho JJD, Wang JJ, Das S, Mitchell N, Oettgen P, Sefton MV, Marsden PA, Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA. Proc Natl Acad Sci U S A, 115(10):2401-2406(2018) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: Long noncoding RNA, Endothelium, Gene Regulations |
Contact List
Philip A. Marsden |
contact affiliation | Institute of Medical Science, University of Toronto |
contact email | p.marsden@utoronto.ca |
lab head | |
Jonathan Krieger |
contact affiliation | SickKids/University of Toronto |
contact email | Jonathan.krieger@sickkids.ca |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD008581
- Label: PRIDE project
- Name: Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNAAngiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA