LIN28A activates the transcription of NANOG in dairy goat male germline stem cells. Issue 6 (14th October 2018)

• Record Type: Journal Article
• Authors: Ma, Fanglin; Du, Xiaomin; Wei, Yudong; Zhou, Zhe; Clotaire, Daguia Zambe John; Li, Na; Peng, Sha; Li, Guangpeng; Hua, Jinlian
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 6(2019:Jun.)
• Page Start: 8113
• Page End: 8121
• Publication Date: 2018-10-14
• Subjects: epigenetic modifications -- GmGSCs -- LIN28A -- NANOG promoter -- TET1; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27593
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: LIN28A serves as a crucial marker of dairy goat male germline stem cells (GmGSCs). In our previous study, we demonstrated that LIN28A promotes proliferation, self‐renewal, and maintains the stemness of GmGSCs. Here, we found that LIN28A could activate the transcription of NANOG in a let‐7g independent manner. We cloned the 5′ upstream of two NANOG genes which were located on chromosome 15 ( NANOG‐ch15 ) and chromosome 5 ( NANOG‐ch5 ), respectively, and then examined their promoter activities and promoter methylation levels. Results showed that NANOG‐ch15 is a pseudogene whereas NANOG‐ch5 is active in Capra hircus . Bioinformatics analysis indicated that the 5′ upstream region of NANOG‐ch5 does not have typical CpG islands but contains several CG enrichment regions and several LIN28A binding sites. Deletion analysis suggested that NANOG‐ch5 promoter can be activated by LIN28A directly binding to the site ‐210 but not by the indirect effect from the inhibition of let‐7g, which is known to be downregulated by LIN28A . Mechanistically, LIN28A recruits and interacts with 5‐methylcytosine‐dioxygenase Ten‐Eleven translocation 1 (TET1) to NANOG‐ch5 gene promoter binding sites to orchestrate 5‐methylcytosine and 5‐hydroxymethylcytosine dynamics. These results revealed the role of LIN28A in NANOG transcriptional regulation via epigenetic DNA modifications to maintain the stemness of GmGSC. Abstract : In this study, we found that LIN28A in a let‐7g independent manner activating the transcription of NANOG that located on chromosome 5 via binding the −573/+210 5′ upstream region. Mechanistically, LIN28A recruits and interacts with 5‐methylcytosine‐dioxygenase Ten‐Eleven translocation 1 (TET1) to NANOG gene promoter binding sites to orchestrate 5‐methylcytosine and 5‐hydroxymethylcytosine dynamics. These results reveal the role of LIN28A in NANOG transcriptional regulation via epigenetic DNA modifications to maintain stemness of goat male germline stem cells (GmGSCs).