细胞凋亡反应中NOXA基因启动子发挥增强子功能调节BCL2基因表达

doi:10.16288/j.yczz.20-213

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Hereditas(Beijing) ›› 2020, Vol. 42 ›› Issue (11): 1110-1121.doi: 10.16288/j.yczz.20-213

• Research Article • Previous Articles Next Articles

The NOXA promoter could function as an active enhancer to regulate the expression of BCL2 in the apoptosis response

Zhongyong Qin^1,², Xiao Shi^1,², Pingping Cao^1,², Ying Chu^1,², Wei Guan⁴, Nan Yang^1,³, He Cheng^1,²(), Yujie Sun^1,²()

^1. Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China
^2. Department of Cell Biology, Nanjing Medical University, Nanjing 211166, China
^3. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, China
^4. The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029,China

Received:2020-07-07 Revised:2020-10-04 Online:2020-11-20 Published:2020-11-06
Contact: Cheng He,Sun Yujie E-mail:chenghe@njmu.edu.cn;yujiesun@njmu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China Nos(81172091);Supported by the National Natural Science Foundation of China Nos(81572789)

Abstract

Abstract:

The transcription of eukaryotic genes is regulated by both proximal promoters and distal enhancers. Some promoters also have enhancer activity. NOXA and BCL2 are pro-apoptotic and anti-apoptotic members of the BCL2 family of protein, respectively. Our previous study has found that the NOXA gene promoter and the BCL2 gene promoter interact at the level of three-dimensional chromatin structure. Moreover, the NOXA gene promoter region displays histone modifications characteristic of both promoters and enhancers. This study aimed to explore whether and when the NOXA promoter could act as an active enhancer to regulate BCL2 expression. Based on the apoptosis model of MCF-7 cells induced by camptothecin, we used chromosome conformation capture (3C), quantitative real-time PCR (qRT-PCR) and the luciferase reporter gene technology to demonstrate that the NOXA promoter could function as an active enhancer and physically interact with the BCL2 promoter through chromatin looping. The regulatory properties of the NOXA promoter were closely related to the strength of the apoptosis stimulation. Under weak apoptotic stimulation (1 μmol/L camptothecin treatment), the NOXA promoter mainly functioned as an enhancer; with the enhancement of apoptotic stimulation (10 μmol/L camptothecin treatment), the NOXA promoter activity increased and mainly regulated the expression of the gene itself to promote apoptosis. Chromatin immunoprecipitation (ChIP) confirmed that the dynamic changes of the promoter activity and enhancer activity in the NOXA promoter region are consistent with its histone modification marks. This study provides new clues for further exploring the mechanism underlying cooperative response of BCL2 family member to apoptosis stimuli.

Key words: NOXA promoter, enhancer, dual transcription regulation function, BCL2 gene, apoptosis

Zhongyong Qin, Xiao Shi, Pingping Cao, Ying Chu, Wei Guan, Nan Yang, He Cheng, Yujie Sun. The NOXA promoter could function as an active enhancer to regulate the expression of BCL2 in the apoptosis response[J]. Hereditas(Beijing), 2020, 42(11): 1110-1121.

Figures/Tables 4

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The NOXA promoter could function as an active enhancer to regulate the expression of BCL2 in the apoptosis response

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