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BioMed Research International
Volume 2018, Article ID 5473725, 9 pages
Research Article

Oncogenic N-Ras Stimulates SRF-Mediated Transactivation via H3 Acetylation at Lysine 9

1School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea
2Hazardous Substances Analysis Division, Seoul Regional Food and Drug Administration, Ministry of Food and Drug Safety, Seoul 07978, Republic of Korea
3Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 46241, Republic of Korea

Correspondence should be addressed to Byung H. Jhun; and Kyunghwan Kim;

Received 19 August 2017; Revised 18 October 2017; Accepted 21 November 2017; Published 3 January 2018

Academic Editor: Andrey Cherstvy

Copyright © 2018 Sun-Ju Yi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Signal transduction pathways regulate the gene expression by altering chromatin dynamics in response to mitogens. Ras proteins are key regulators linking extracellular stimuli to a diverse range of biological responses associated with gene regulation. In mammals, the three ras genes encode four Ras protein isoforms: H-Ras, K-Ras4A, K-Ras4B, and N-Ras. Although emerging evidence suggests that Ras isoforms differentially regulate gene expressions and are functionally nonredundant, the mechanisms underlying Ras specificity and Ras signaling effects on gene expression remain unclear. Here, we show that oncogenic N-Ras acts as the most potent regulator of SRF-, NF-κB-, and AP-1-dependent transcription. N-Ras-RGL2 axis is a distinct signaling pathway for SRF target gene expression such as Egr1 and JunB, as RGL2 Ras binding domain (RBD) significantly impaired oncogenic N-Ras-induced SRE activation. By monitoring the effect of Ras isoforms upon the change of global histone modifications in oncogenic Ras-overexpressed cells, we discovered that oncogenic N-Ras elevates H3K9ac/H3K23ac levels globally in the chromatin context. Importantly, chromatin immunoprecipitation (ChIP) assays revealed that H3K9ac is significantly enriched at the promoter and coding regions of Egr1 and JunB. Collectively, our findings define an undocumented role of N-Ras in modulating of H3 acetylation and in gene regulation.