XCI-escaping gene KDM5C contributes to ovarian development via downregulating miR-320a

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• 作者：Yi-Xi Sun ; Yi-Xin Zhang ; Dan Zhang ; Chen-Ming Xu ; Song-Chang Chen…
• 刊名：Human Genetics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：136
• 期：2
• 页码：227-239
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Human Genetics; Molecular Medicine; Gene Function; Metabolic Diseases;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-1203
• 卷排序：136

文摘

Mechanisms underlying female gonadal dysgenesis remain unclarified and relatively unstudied. Whether X-chromosome inactivation (XCI)-escaping genes and microRNAs (miRNAs) contribute to this condition is currently unknown. We compared 45,X Turner Syndrome women with 46,XX normal women, and investigated differentially expressed miRNAs in Turner Syndrome through plasma miRNA sequencing. We found that miR-320a was consistently upregulated not only in 45,X plasma and peripheral blood mononuclear cells (PBMCs), but also in 45,X fetal gonadal tissues. The levels of miR-320a in PBMCs from 45,X, 46,XX, 46,XY, and 47,XXY human subjects were inversely related to the expression levels of XCI-escaping gene KDM5C in PBMCs. In vitro models indicated that KDM5C suppressed miR-320a transcription by directly binding to the promoter of miR-320a to prevent histone methylation. In addition, we demonstrated that KITLG, an essential gene for ovarian development and primordial germ cell survival, was a direct target of miR-320a and that it was downregulated in 45,X fetal gonadal tissues. In conclusion, we demonstrated that downregulation of miR-320a by the XCI-escaping gene KDM5C contributed to ovarian development by targeting KITLG.