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KDM5D-mediated H3K4 demethylation is required for sexually dimorphic gene expression in mouse embryonic fibroblasts
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- Hayase Mizukami
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)
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- Jun-Dal Kim
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)
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- Saori Tabara
- College of Agro-Biological Resource Sciences
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- Weizhe Lu
- Ph.D. Program in Human Biology, School of Integrative Global Majors (SIGMA)
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- Chulwon Kwon
- Graduate School of Life and Environmental Sciences
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- Misaki Nakashima
- Graduate School of Life and Environmental Sciences
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- Akiyoshi Fukamizu
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)
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Description
Males and females share the same genetic code, but gene expression profile often displays differences between two sexes. Mouse embryonic fibroblasts (MEFs) have been used to experiment as a useful tool to test gene function. They have also been characterized by gender-based differences in expressed genes such as Y-linked Sry or X-linked Hprt. However, there is no report on sex differences in global gene expression. Here, using the next-generation RNA sequencing, we compared the comprehensive transcriptome of MEFs derived from two sexes. In comparison with the female group, the male group up-regulated 27 differentially expressed genes (DEGs), in which a male-specific histone demethylase KDM5D gene is included, and 7 DEGs were down-regulated. Based on the results by searching the ENCODE analysis, it was shown that the expression of 15 genes identified is potentially regulated by the methylation of H3K4me1 or H3K4me3. Interestingly, we demonstrated that both of H3K4 methylation are induced by knocking down KDM5D, which causes changes in patterns of eight DEGs found in male MEFs. Collectively, these data not only suggest an importance of KDM5D-mediated demethylation of H3K4 involved in the sexually dimorphic gene expression in male MEFs, but also may provide information regarding sex-dependent changes in gene expression when MEFs are used for experiments.
Journal
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- The Journal of Biochemistry
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The Journal of Biochemistry 165 (4), 335-342, 2018-12-24
Oxford University Press (OUP)