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@article{Dryden:2012:10.1074/jbc.M112.346791,
author = {Dryden, NH and Sperone, A and Martin-Almedina, S and Hannah, RL and Birdsey, GM and Khan, ST and Layhadi, JA and Mason, JC and Haskard, DO and Goettgens, B and Randi, AM},
doi = {10.1074/jbc.M112.346791},
journal = {Journal of Biological Chemistry},
pages = {12331--12342},
title = {The transcription factor erg controls endothelial cell quiescence by repressing activity of Nuclear Factor (NF)-kappa B p65},
url = {http://dx.doi.org/10.1074/jbc.M112.346791},
volume = {287},
year = {2012}
}

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TY  - JOUR
AB  - The interaction of transcription factors with specific DNA sequences is critical for activation of gene expression programs. In endothelial cells (EC), the transcription factor NF-κB is important in the switch from quiescence to activation, and is tightly controlled to avoid excessive inflammation and organ damage. Here we describe a novel mechanism that controls the activation of NF-κB in EC. The transcription factor Erg, the most highly expressed ETS member in resting EC, controls quiescence by repressing proinflammatory gene expression. Focusing on intercellular adhesion molecule 1(ICAM)-1 as a model, we identify two ETS binding sites (EBS −118 and −181) within the ICAM-1 promoter required for Erg-mediated repression. We show that Erg binds to both EBS −118 and EBS −181, the latter located within the NF-κB binding site. Interestingly, inhibition of Erg expression in quiescent EC results in increased NF-κB-dependent ICAM-1 expression, indicating that Erg represses basal NF-κB activity. Erg prevents NF-κB p65 from binding to the ICAM-1 promoter, suggesting a direct mechanism of interference. Gene set enrichment analysis of transcriptome profiles of Erg and NF-κB-dependent genes, together with chromatin immunoprecipitation (ChIP) studies, reveals that this mechanism is common to other proinflammatory genes, including cIAP-2 and IL-8. These results identify a role for Erg as a gatekeeper controlling vascular inflammation, thus providing an important barrier to protect against inappropriate endothelial activation.
AU  - Dryden,NH
AU  - Sperone,A
AU  - Martin-Almedina,S
AU  - Hannah,RL
AU  - Birdsey,GM
AU  - Khan,ST
AU  - Layhadi,JA
AU  - Mason,JC
AU  - Haskard,DO
AU  - Goettgens,B
AU  - Randi,AM
DO  - 10.1074/jbc.M112.346791
EP  - 12342
PY  - 2012///
SN  - 0021-9258
SP  - 12331
TI  - The transcription factor erg controls endothelial cell quiescence by repressing activity of Nuclear Factor (NF)-kappa B p65
T2  - Journal of Biological Chemistry
UR  - http://dx.doi.org/10.1074/jbc.M112.346791
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000302782200072&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.sciencedirect.com/science/article/pii/S0021925820531608?via%3Dihub
UR  - http://hdl.handle.net/10044/1/87654
VL  - 287
ER  -

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