Cloning and Transcriptional Activity of the Mouse Omi/HtrA2 Gene Promoter.

Authors

Dan Liu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
Xin Liu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaFollow
Ye Wu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaFollow
Wen Wang, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, ChinaFollow
Xin-Liang Ma, Beijing Key Laboratory of Metabolic Disturbance Related Cardiovascular Disease, Beijing, China; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United StatesFollow
Huirong Liu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Beijing Key Laboratory of Metabolic Disturbance Related Cardiovascular Disease, Beijing, ChinaFollow

Document Type

Article

Publication Date

1-16-2016

Comments

This article has been peer reviewed. It was published in: International Journal of Molecular Science.

Volume 17, Issue 1, 16 January 2016, Article number 119.

The published version is available at DOI: 10.3390/ijms17010119

Copyright © 2016 by the authors; licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).

Abstract

HtrA serine peptidase 2 (HtrA2), also named Omi, is a pro-apoptotic protein that exhibits dramatic changes in expression levels in a variety of disorders, including ischemia/reperfusion injury, cancer, and neurodegeneration. In our study, Omi/HtrA2 protein levels were high in the heart, brain, kidney and liver, with elevated heart/brain expression in aging mice. A similar expression pattern was observed at the mRNA level, which suggests that the regulation of Omi/HtrA2 is predominately transcriptional. Promoter binding by transcription factors is the main influencing factor of transcription, and to identify specific promoter elements that contribute to the differential expression of mouse Omi/HtrA2, we constructed truncated Omi/HtrA2 promoter/luciferase reporter vectors and analyzed their relative luciferase activity; it was greatest in the promoter regions at -1205~-838 bp and -146~+93 bp, with the -838~-649 bp region exhibiting negative regulatory activity. Bioinformatics analysis suggested that the Omi/HtrA2 gene promoter contains a CpG island at -709~+37 bp, and eight heat shock transcription factor 1 (HSF1) sites, two Sp1 transcription factor (SP1)sites, one activator protein (AP) site, seven p53 sites, and four YY1 transcription factor(YY1) sites were predicted in the core areas. Furthermore, we found that p53 and HSF1 specifically binds to the Omi/HtrA2 promoter using chromatin immunoprecipitation analysis. These results provide a foundation for understanding Omi/HtrA2 regulatory mechanisms, which could further understanding of HtrA-associated diseases.

Recommended Citation

Liu, Dan; Liu, Xin; Wu, Ye; Wang, Wen; Ma, Xin-Liang; and Liu, Huirong, "Cloning and Transcriptional Activity of the Mouse Omi/HtrA2 Gene Promoter." (2016). Department of Medicine Faculty Papers. Paper 149.
https://jdc.jefferson.edu/medfp/149

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

26784188