1. Academic Validation
  2. miR-29c-3p promotes alcohol dehydrogenase gene cluster expression by activating an ADH6 enhancer

miR-29c-3p promotes alcohol dehydrogenase gene cluster expression by activating an ADH6 enhancer

  • Biochem Pharmacol. 2022 Sep;203:115182. doi: 10.1016/j.bcp.2022.115182.
Ningning Chen 1 Jiao Luo 1 Yufei Hou 2 Yanan Ji 1 Mengyue Xie 1 Ge Song 1 Dianke Yu 3
Affiliations

Affiliations

  • 1 School of Public Health, Qingdao University, Qingdao, China.
  • 2 Weihai Center for Disease Control and Prevention, Weihai, China.
  • 3 School of Public Health, Qingdao University, Qingdao, China. Electronic address: dianke.yu@qdu.edu.cn.
Abstract

Alcohol dehydrogenases (ADHs) play vital roles in alcohol metabolism and alcohol toxicity, yet little is known about microRNA-mediated regulation of the ADH gene cluster. Here, we showed that miR-29c activated ADH gene cluster transcription by targeting an enhancer element within the ADH6 gene. miR-29c is differentially expressed in alcoholic liver disease. Following biochemical and molecular evidence demonstrated that miR-29c increased ADH6 mRNA and protein levels without affecting the stability of the ADH6 transcript. Further evidence showed that exogenous miR-29c translocated into the nucleus and then unconventionally bound an enhancer element within the ADH6 gene. Luciferase reporter assay and chromatin immunoprecipitation data indicated that miR-29c activated the enhancer and increased the enrichment of RNA polymerase II at the promoter regions of ADH1A, ADH1B, ADH1C, ADH4, and ADH6. Finally, exogenous miR-29c transfection promoted the expression of ADH1A, ADH1B, ADH1C, and ADH4 pre-mRNA and mRNA transcripts from the ADH gene cluster. In conclusion, our data suggest that miR-29c might be a novel epigenetic regulator involved in ADH gene cluster activation.

Keywords

ADH6; Alcohol dehydrogenase gene cluster; Enhancer; Ethanol; miR-29c.

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