Abstract
JmjC domain-containing proteins are a class of enzymes responsible for histone demethylation. Previous studies revealed that the JmjC domain-containing protein KDM3A possesses intrinsic demethylase activity toward lysine 9 of histone H3 and plays essential roles in spermiogenesis. In contrast, the biological roles of JMJD1C, a KDM3A homolog in mice, are largely unknown. Here we present the crucial role of JMJD1C in male gametogenesis. Jmjd1c-deficient males became infertile due to the progressive reduction of germ cells after 3 mo of age. Importantly, Jmjd1c-deficient testes frequently contained abnormal tubules lacking developmentally immature germ cells. JMJD1C is most abundantly expressed in undifferentiated spermatogonia in mouse testis. The numbers of ZBTB16-positive spermatogonia and apoptotic germ cells in Jmjd1c-deficient testes decreased and increased in an age-dependent manner, respectively. Our studies demonstrated that JMJD1C contributes to the long-term maintenance of the male germ line.
Keywords:
aging; epigenetics; histone modifications; male infertility.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult Stem Cells / cytology
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Adult Stem Cells / metabolism*
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Adult Stem Cells / pathology
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Aging*
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Alternative Splicing
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Androstenedione / blood
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Animals
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Animals, Newborn
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Apoptosis*
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Gene Expression Regulation, Enzymologic*
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Infertility, Male / blood
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Infertility, Male / enzymology
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Infertility, Male / metabolism
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Infertility, Male / pathology
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / deficiency
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors
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Jumonji Domain-Containing Histone Demethylases / deficiency
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Jumonji Domain-Containing Histone Demethylases / genetics
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Jumonji Domain-Containing Histone Demethylases / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Mutant Proteins / metabolism
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Spermatogenesis*
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Spermatogonia / cytology
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Spermatogonia / metabolism*
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Spermatogonia / pathology
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Testis / cytology
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Testis / growth & development
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Testis / metabolism
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Testis / pathology
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Testosterone / blood
Substances
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Isoenzymes
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Mutant Proteins
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Testosterone
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Androstenedione
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JMJD1c protein, mouse
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Jumonji Domain-Containing Histone Demethylases