PXD008581

PXD008581 is an original dataset announced via ProteomeXchange.

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

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.

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]

curator keyword: Biological

submitter keyword: Long noncoding RNA, Endothelium, Gene Regulations

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/02/PXD008581

PRIDE project URI

• PRIDE
  1. PXD008581
     1. Label: PRIDE project
     2. Name: Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNAAngiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA