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.
CITATION STYLE
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
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