The transcription factor Erg controls endothelial cell quiescence by repressing activity of nuclear factor (NF)-κB p65.

The Journal of Biological Chemistry
Nicola H DrydenA M Randi

Abstract

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 (ChI...Continue Reading

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Citations

Aug 7, 2013·Molecular Cancer·Bastian Hoesel, Johannes A Schmid
Jun 11, 2015·Organogenesis·Rong HanMaria Trojanowska
Oct 8, 2016·Molecular BioSystems·Matthias G BeuerleIan R Gould
Feb 15, 2019·Circulation Research·Amélie PinardDianna M Milewicz
Aug 1, 2013·Physiological Reviews·Paul N Hopkins
Nov 7, 2019·Human Molecular Genetics·Judith MarsmanGregory T Jones
Nov 6, 2012·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Dorian O HaskardAnna M Randi
Feb 20, 2019·Frontiers in Immunology·Marion MussbacherJohannes A Schmid
Jul 25, 2019·Scientific Reports·Xiang LiuSarah Thayer
Jan 25, 2017·Oxidative Medicine and Cellular Longevity·Simón Quetzalcoatl Rodríguez-LaraLeonel García-Benavides
Sep 22, 2016·The Journal of Biological Chemistry·Sébastien PinteFabrice Soncin
Aug 6, 2021·Journal of Shoulder and Elbow Surgery·Joshua A GordonGeorge R Dodge

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Methods Mentioned

BETA
Immunoprecipitation
PCR
Assay
ChIP
electrophoretic mobility shift assay
transcription profiling

Software Mentioned

Gene Set Enrichment Analysis
GSEA
MatInspector

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