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. 2019 Aug;294(4):1023-1036.
doi: 10.1007/s00438-019-01560-0. Epub 2019 Apr 10.

Transcriptional regulation of the porcine miR-17-92 cluster

Xiu-Qin Yang  1 , Cai-Xia Zhang  2 , Jin-Kui Wang  2 , Liang Wang  3 , Xin Du  2 , Yan-Fang Song  2 , Di Liu  4
Affiliations

Transcriptional regulation of the porcine miR-17-92 cluster

Xiu-Qin Yang et al. Mol Genet Genomics. 2019 Aug.

Abstract

The miR-17-92 cluster has been involved in the cell cycle, apoptosis, and signaling. However, its transcriptional regulation has not been fully characterized. To elucidate the transcriptional regulation, the promoter of miR-17-92 was analyzed in detail in pig here. We found that, as an intronic miRNA, porcine miR-17-92 cluster was regulated by two independent promoters, an A/T-rich region directly upstream of the miR-17-92 coding sequence, and a G/C-rich region corresponding to the host gene promoter of the human miR-17-92 cluster. Several cis-regulatory elements were identified including sites for c-Myc, NFY, E2F3, and SP1, among which NFY and c-Myc sites were present in both A/T- and G/C-rich regions, while E2F3 and SP1 sites only existed in G/C-rich region. Sites for c-Myc, E2F3, and SP1 were positive for regulating transcription. NFY sites played bipartite roles, functioning as a repressor for the A/T-rich region, and as an activator for the G/C-rich region. Additionally, we found that levels of individual miRNAs in the cluster were not promoted completely in parallel with each other or with pri-miR-17-92 by the A/T-rich region, through using a self-made vector by modifying pGL3-basic in which firefly luciferase gene was replaced with an miR-17-92 cluster and a direct upstream A/T-rich region. The expression regulation of miR-17-92 is complicated and the results will contribute to further revealing the regulatory mechanisms under the expression of the miR-17-92 cluster.

Keywords: Pig; Promoter; Transcription factor; cis-regulatory element; miR-17-92 cluster.

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