JMJD1C Exhibits Multiple Functions in Epigenetic Regulation during Spermatogenesis

• Published in: PloS one 2016-09, Vol.11 (9), p.e0163466-e0163466
• Main Authors: Nakajima, Ryusuke, Okano, Hideyuki, Noce, Toshiaki
• Format: Article
• Language: English
• Subjects: Acetylation; Analysis; Animals; Biology and Life Sciences; Cell self-renewal; Chromatin; Chromatin remodeling; Cloning; Deoxyribonucleic acid; DNA; DNA methylation; Elongation; Epigenesis, Genetic; Epigenetic inheritance; Epigenetics; Gene expression; Genes; Genetic engineering; Heat shock proteins; Histones; Histones - metabolism; Hsp90 protein; Jumonji Domain-Containing Histone Demethylases - genetics; Jumonji Domain-Containing Histone Demethylases - metabolism; Leukemia; Male; Medicine and Health Sciences; Mice; Mice, Transgenic; Mutation; Nanog Homeobox Protein - genetics; Nanog Homeobox Protein - metabolism; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Physiology; Proteins; Research and analysis methods; Rodents; Spermatids; Spermatogenesis; Spermatogenesis - genetics; Spermatogonia; Spermatogonia - metabolism; Stem cells; Testes; Testis - metabolism; Transgenic mice
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0163466

Jmjd1C is one of the Jmjd1 family genes that encode putative demethylases against histone H3K9 and non-histone proteins and has been proven to play an indispensable role in mouse spermatogenesis. Here, we analyzed a newly-bred transgenic mouse strain carrying a Jmjd1C loss-of-function allele in which a β-geo cassette was integrated into the intron of the Jmjd1C locus. Jmjd1C gene-trap homozygous testes exhibited malformations in postmeiotic processes and a deficiency in the long-term maintenance of undifferentiated spermatogonia. Some groups of spermatids in the homozygous testis showed abnormal organization and incomplete elongation from the first wave of spermatogenesis onwards. Moreover, histone H4K16 acetylation, which is required for the onset of chromatin remodeling, appeared to be remarkably decreased. These effects may not have been a result of the drastic decrease in gene expression related to the events but instead may have been due to the lack of interaction between JMJD1C and its partner proteins, such as MDC1 and HSP90. Additionally, significant decreases in Oct4 expression and NANOG- and OCT4-expressing spermatogonia were found in the Jmjd1C homozygous mature testis, suggesting that JMJD1C may participate in the maintenance of spermatogonial stem cell self-renewal by up-regulating Oct4 expression. These results indicate that JMJD1C has multiple functions during spermatogenesis through interactions with different partners during the spermatogenic stages.