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LIN28A activates the transcription of NANOG in dairy goat male germline stem cells
Author(s) -
Ma Fanglin,
Du Xiaomin,
Wei Yudong,
Zhou Zhe,
Clotaire Daguia Zambe John,
Li Na,
Peng Sha,
Li Guangpeng,
Hua Jinlian
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27593
Subject(s) - homeobox protein nanog , promoter , biology , epigenetics , dna methylation , transcription factor , germline , rex1 , microbiology and biotechnology , methylation , gene , genetics , embryonic stem cell , gene expression , induced pluripotent stem cell
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.