Phosphorylation and acetylation of histone H3 and autoregulation by early growth response 1 mediate interleukin 1β induction of early growth response 1 transcription

44Citations
Citations of this article
40Readers
Mendeley users who have this article in their library.

Abstract

Objective-The transcription factor early growth response (EGR)-1 has been implicated as a key vascular phenotypic switch through its control of inducible transcription. EGR-1 autoregulation, and histone modification in the EGR-1 promoter, represent key mechanisms in EGR-1 control, but have not been explored. Methods and Results-We demonstrate that EGR-1 regulates its own transcription and that this involves histone H3 phosphorylation and acetylation. EGR-1 transactivates its promoter in smooth muscle cells exposed to interleukin (IL) 1β through a novel cis-acting element (-211/-203). PD98059, which inhibits mitogen-activated protein kinase kinase/extracellular regulated kinase (MEK/ERK) attenuates IL-1β-inducible phosphorylation of extracellular signal-regulated kinase 1/2 and mitogen and stress-activated protein kinases 1/2; and reduces levels of phosphorylated and acetylated histone H3. Histone deacetylase inhibition enhances EGR-1 transcription in response to cytokine. Conversely, suppression of histone modification with mitogen and stress-activated protein kinase 1/2 short interfering RNA, or the histone H3 acetyltransferase inhibitor Garcinol, inhibits IL-1β-inducible EGR-1 transcription. EGR-1 interacts with the acetyltransferase p300. Acetylated H3 and phosphorylated H3 are enriched at the promoter of EGR-1; and EGR-1 is enriched at the promoters of tissue factor and plasminogen activator inhibitor 1 in response to IL-1β, and attenuated by PD98059, Garcinol, and mitogen and stress-activated protein kinase 1/2 short interfering RNA. Conclusion-IL- 1β induction of EGR-1 transcription involves histone H3 phosphorylation, acetylation, and autoregulation by EGR-1. © 2010 American Heart Association, Inc.

Cite

CITATION STYLE

APA

Wang, B., Chen, J., Santiago, F. S., Janes, M., Kavurma, M. M., Chong, B. H., … Khachigian, L. M. (2010). Phosphorylation and acetylation of histone H3 and autoregulation by early growth response 1 mediate interleukin 1β induction of early growth response 1 transcription. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(3), 536–545. https://doi.org/10.1161/ATVBAHA.109.193821

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free