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Role of Nkx2.5 in H2O2-induced Nsd1 suppression

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Cell Stress and Chaperones Aims and scope

Abstract

Nuclear receptor–binding SET domain–containing protein 1 (Nsd1) acts as a histone lysine methyltransferase, and its role in oxidative stress–related abnormal embryonic heart development remains poorly understood. In the present study, H2O2 decreased the expression of Nsd1 and NK2 transcription factor related locus 5 (Nkx2.5). We further focused on Nkx2.5 modulating the transcription of Nsd1 in response to H2O2. Luciferase activity analysis indicated that a regulatory region from − 646 to − 282 is essential for the basal transcriptional activity, in which, an a Nkx2.5-binding element (NKE) was identified at − 412/− 406 of the Nsd1 promoter by electrophoresis mobility shift assay and a chromatin immunoprecipitation assay. H2O2 obviously reduced the p646-luc promoter activity, and the depletion of Nkx2.5 expression weakened H2O2 inhibition on the p646-luc promoter. The overexpression of Nkx2.5 increase Nsd1 p646-luc promoter activity, but did not affected p646-luc-mut. Furthermore, overexpression and depletion of Nkx2.5 led to the increase and decrease of Nsd1 protein and mRNA levels. These data indicated that H2O2-induced Nsd1 suppression resulted from the decrease of Nkx2.5 expression through the NKE element.

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Authors and Affiliations

  1. Department of Clinical Genetics, China Medical University, No.36 San Hao Street, Shenyang, 110004, Liaoning, China

    Xiaoyan Liang, Guoming Chu, Leitong Wang, Guangrui Lai & Yanyan Zhao

  2. Central Laboratory, Binzhou People’s Hospital, Binzhou, 256600, Shandong, China

    Xiaoyan Liang

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  1. Xiaoyan Liang
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  2. Guoming Chu
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  3. Leitong Wang
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  4. Guangrui Lai
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  5. Yanyan Zhao
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Correspondence to Yanyan Zhao.

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All experiments conformed to the guide for the care and use of laboratory animals and were approved by the Ethics Committee of Shengjing Hospital (Ethic approval no. 2017PS216K, Shenyang, China).

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Liang, X., Chu, G., Wang, L. et al. Role of Nkx2.5 in H2O2-induced Nsd1 suppression. Cell Stress and Chaperones 24, 697–707 (2019). https://doi.org/10.1007/s12192-019-00995-z

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  • DOI: https://doi.org/10.1007/s12192-019-00995-z

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