Genomics

Dataset Information

300

Physiological Vascular Permeability Requires Induction of Endothelial NR4A1 by Progesterone Receptor [ChIP-Seq]


ABSTRACT: Vascular permeability is frequently associated with inflammation and it is triggered by chemokines and by a cohort of secreted permeability factors, such as VEGF. In contrast, here we showed that the physiological vascular permeability that precedes implantation is directly controlled by progesterone receptor (PR) and it is independent of VEGF. Both global and endothelial-specific deletion of PR block physiological vascular permeability in the uterus while misexpression of PR in the endothelium of other organs results in ectopic vascular leakage. Integration of genome-wide transcriptional profile of endothelium and ChIP-sequencing revealed that PR induces a NR4A1 (Nur77/TR3) specific transcriptional program that broadly regulates vascular permeability in response to progesterone. This program triggers concurrent suppression of several junctional proteins and leads to an effective, timely and venule-specific regulation of vascular barrier function. Silencing NR4A1 blocks PR-mediated permeability responses indicating a direct link between PR and NR4A1. These results reveal a previously unknown function for progesterone receptor on endothelial cell biology with consequences to physiological vascular permeability and implications to the clinical use of progestins and anti-progestins on blood vessel integrity. Examination of PR binding sites in HUVEC cells using ChIP-seq (non-infected-negative control, PR infected followed by ligand treatment-PR+P or vehicle PR)

ORGANISM(S): Homo sapiens  

SUBMITTER: Thomas J Murphy   Hanna K Mikkola  Peter Tontonoz  Tonis Org  Nancy C Allen  Lauren Goddard  Lauren A Sanchez  Carmen M Warren  M L Iruela-Arispe  Josephine M Enciso  Minako K Hashimoto-Partyka 

PROVIDER: E-GEOD-43786 | ArrayExpress | 2014-01-01

SECONDARY ACCESSION(S): GSE43786SRP018235PRJNA187478

REPOSITORIES: GEO, ArrayExpress, ENA

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