The elucidation of the mechanism of Kdm5a, the histone demethylase, in the testicular function

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K20101
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: Nishio Hidenori 名古屋市立大学, 大学院医学研究科, 研究員 (10621063)
• Research Collaborator: HAYASHI Yutaro ; MIZUNO Kentaro ; KUROKAWA Satoshi ; KAMISAWA Hideyuki ; MORITOKI Yoshinobu
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ヒストン修飾 / 精子幹細胞 / エピジェネティクス

Outline of Final Research Achievements

In this study, we generated Kdm5a-gfp expression vectors and transfected the vector into GC-1 cells, which is a mouse spermatogonial cell line. By using microarray analysis, we identified genes that were altered by Kdm5a expression. The microarray analysis revealed high expression levels of Tet1, Btc, and Scml2, and low expression levels of Wnt1, Sox6, and Sox8 in cells transfected with Kdm5a-gfp. The ChIP-qPCR assay with H3K4me3 antibody showed that the expression level of Scml2 was higher in the Kdm5a-transfected cells.
Moreover, human undescended testes were evaluated by double immunofluorescence staining. The expression of H3K4me2/me3 decreased in the cells which KDM5A expressed strongly, while the expression of H3K4me1 increased in the cells which KDM5A expressed weakly.
Therefore, we suggest that Kdm5a is involved in differentiation in the early stages of spermatogenesis by simultaneous regulation of gene expressions by demethylating histone H3K4.

Free Research Field

泌尿器科学