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Kdm6a overexpression improves the development of cloned mouse embryos

Published online by Cambridge University Press:  14 December 2017

Guang-yu Bai
Affiliation:
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Si-hang Song
Affiliation:
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Yu-wei Zhang
Affiliation:
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Xiang Huang
Affiliation:
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Xing-wei Huang
Affiliation:
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Rui-zhen Sun
Affiliation:
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Lei Lei
Affiliation:
Department of Histology and Embryology, Harbin Medical University, Harbin 150081, China.
Corresponding
E-mail address:

Summary

Somatic cell nuclear transfer (SCNT) is an important technique for life science research. However, most SCNT embryos fail to develop to term due to undefined reprogramming defects. Here, we show that abnormal Xi occurs in somatic cell NT blastocysts, whereas in female blastocysts derived from cumulus cell nuclear transfer, both X chromosomes were inactive. H3K27me3 removal by Kdm6a mRNA overexpression could significantly improve preimplantation development of NT embryos, and even reached a 70.2% blastocyst rate of cleaved embryos compared with the 38.5% rate of the control. H3K27me3 levels were significantly reduced in blastomeres from cloned blastocysts after overexpression of Kdm6a. qPCR indicated that rDNA transcription increased in both NT embryos and 293T cells after overexpression of Kdm6a. Our findings demonstrate that overexpression of Kdm6a improved the development of cloned mouse embryos by reducing H3K27me3 and increasing rDNA transcription.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

3

These authors contributed equally to this work.

References

Bai, G.Y., Song, S.H., Wang, Z.D., Shan, Z.Y., Sun, R.Z., Liu, C.J., Wu, Y.S., Li, T. & Lei, L. (2016). Embryos aggregation improves development and imprinting gene expression in mouse parthenogenesis. Dev. Growth Differ. 58, 270–9.CrossRefGoogle ScholarPubMed
Bai, G.Y., Song, S.H., Sun, R.Z., Zhang, Z.H., Li, J., Wang, Z.D., Liu, Z.H. & Lei, L. (2017). RNAi-mediated knockdown of Parp1 does not improve the development of female cloned mouse embryos. Oncotarget 8, 69863–73.CrossRefGoogle Scholar
Berletch, J.B., Deng, X., Nguyen, D.K. & Disteche, C.M. (2013). Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A. PLoS Genet. 9, e1003489.CrossRefGoogle ScholarPubMed
Bogershausen, N., Gatinois, V., Riehmer, V., Kayserili, H., Becker, J., Thoenes, M., Simsek-Kiper, P.O., Barat-Houari, M., Elcioglu, N.H., Wieczorek, D., Tinschert, S., Sarrabay, G., Strom, T.M., Fabre, A., Baynam, G., Sanchez, E., Nurnberg, G., Altunoglu, U., Capri, Y., Isidor, B., Lacombe, D., Corsini, C., Cormier-Daire, V., Sanlaville, D., Giuliano, F., Le Quan Sang, K.H., Kayirangwa, H., Nurnberg, P., Meitinger, T., Boduroglu, K., Zoll, B., Lyonnet, S., Tzschach, A., Verloes, A., Di Donato, N., Touitou, I., Netzer, C., Li, Y., Genevieve, D., Yigit, G. & Wollnik, B. (2016). Mutation update for Kabuki syndrome genes KMT2D and KDM6A and further delineation of X-linked Kabuki syndrome subtype 2. Hum. Mutat. 37, 847–64.CrossRefGoogle ScholarPubMed
Cho, Y.W., Hong, T., Hong, S., Guo, H., Yu, H., Kim, D., Guszczynski, T., Dressler, G.R., Copeland, T.D., Kalkum, M. & Ge, K. (2007). PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex. J. Biol. Chem. 282, 20395–406.CrossRefGoogle ScholarPubMed
Dantzer, F. & Santoro, R. (2013). The expanding role of PARPs in the establishment and maintenance of heterochromatin. FEBS J. 280, 3508–18.CrossRefGoogle ScholarPubMed
Dunford, A., Weinstock, D.M., Savova, V., Schumacher, S.E., Cleary, J.P., Yoda, A., Sullivan, T.J., Hess, J.M., Gimelbrant, A.A., Beroukhim, R., Lawrence, M.S., Getz, G. & Lane, A.A. (2016). Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias. Nat. Genet. 49, 1016.CrossRefGoogle ScholarPubMed
Gong, F., Clouaire, T., Aguirrebengoa, M., Legube, G. & Miller, K.M. (2017). Histone demethylase KDM5A regulates the ZMYND8-NuRD chromatin remodeler to promote DNA repair. J. Cell Biol. 216, 1959–74.CrossRefGoogle ScholarPubMed
He, R. & Kidder, B.L. (2017). H3K4 demethylase KDM5B regulates global dynamics of transcription elongation and alternative splicing in embryonic stem cells. Nucleic Acids Res. 45, 6427–41.CrossRefGoogle ScholarPubMed
Hormanseder, E., Simeone, A., Allen, G.E., Bradshaw, C.R., Figlmuller, M., Gurdon, J. & Jullien, J. (2017). H3K4 methylation-dependent memory of somatic cell identity inhibits reprogramming and development of nuclear transfer embryos. Cell Stem Cell 21, 135–43, e136.CrossRefGoogle ScholarPubMed
Inoue, K., Kohda, T., Sugimoto, M., Sado, T., Ogonuki, N., Matoba, S., Shiura, H., Ikeda, R., Mochida, K., Fujii, T., Sawai, K., Otte, A.P., Tian, X.C., Yang, X., Ishino, F., Abe, K. & Ogura, A. (2010). Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer. Science 330, 496–9.CrossRefGoogle ScholarPubMed
Issaeva, I., Zonis, Y., Rozovskaia, T., Orlovsky, K., Croce, C.M., Nakamura, T., Mazo, A., Eisenbach, L. & Canaani, E. (2007). Knockdown of ALR (MLL2). reveals ALR target genes and leads to alterations in cell adhesion and growth. Mol. Cell. Biol. 27, 1889–903.CrossRefGoogle ScholarPubMed
Jullien, J., Vodnala, M., Pasque, V., Oikawa, M., Miyamoto, K., Allen, G., David, S.A., Brochard, V., Wang, S., Bradshaw, C., Koseki, H., Sartorelli, V., Beaujean, N. & Gurdon, J. (2017). Gene resistance to transcriptional reprogramming following nuclear transfer is directly mediated by multiple chromatin-repressive pathways. Mol. Cell 65, 873–84, e878.CrossRefGoogle ScholarPubMed
Kuang, Y., Lu, F., Guo, J., Xu, H., Wang, Q., Xu, C., Zeng, L. & Yi, S. (2017). Histone demethylase KDM2B upregulates histone methyltransferase EZH2 expression and contributes to the progression of ovarian cancer in vitro and in vivo . OncoTargets Ther. 10, 3131–44.CrossRefGoogle ScholarPubMed
Liu, X., Wang, C., Liu, W., Li, J., Li, C., Kou, X., Chen, J., Zhao, Y., Gao, H., Wang, H., Zhang, Y., Gao, Y. & Gao, S. (2016). Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos. Nature 537, 558–62.CrossRefGoogle ScholarPubMed
Matoba, S., Inoue, K., Kohda, T., Sugimoto, M., Mizutani, E., Ogonuki, N., Nakamura, T., Abe, K., Nakano, T., Ishino, F. & Ogura, A. (2011). RNAi-mediated knockdown of Xist can rescue the impaired postimplantation development of cloned mouse embryos. Proc. Natl. Acad. Sci. USA 108, 20621–6.CrossRefGoogle ScholarPubMed
Matoba, S., Liu, Y., Lu, F., Iwabuchi, K.A., Shen, L., Inoue, A. & Zhang, Y. (2014). Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation. Cell 159, 884–95.CrossRefGoogle ScholarPubMed
Oikawa, M., Matoba, S., Inoue, K., Kamimura, S., Hirose, M., Ogonuki, N., Shiura, H., Sugimoto, M., Abe, K., Ishino, F. & Ogura, A. (2013). RNAi-mediated knockdown of Xist does not rescue the impaired development of female cloned mouse embryos. J. Reprod. Dev. 59, 231–7.CrossRefGoogle Scholar
Plath, K., Fang, J., Mlynarczyk-Evans, S.K., Cao, R., Worringer, K.A., Wang, H., de la Cruz, C.C., Otte, A.P., Panning, B. & Zhang, Y. (2003). Role of histone H3 lysine 27 methylation in X inactivation. Science 300, 131–5.CrossRefGoogle ScholarPubMed
Shpargel, K.B., Starmer, J., Yee, D., Pohlers, M. & Magnuson, T. (2014). KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development. PLoS Genetics 10, e1004507.CrossRefGoogle ScholarPubMed
Suzuki, T., Minami, N., Kono, T. & Imai, H. (2006). Zygotically activated genes are suppressed in mouse nuclear transferred embryos. Cloning Stem Cells 8, 295304.CrossRefGoogle ScholarPubMed
Swigut, T. & Wysocka, J. (2007). H3K27 demethylases, at long last. Cell 131, 2932.CrossRefGoogle ScholarPubMed
Van Laarhoven, P.M., Neitzel, L.R., Quintana, A.M., Geiger, E.A., Zackai, E.H., Clouthier, D.E., Artinger, K.B., Ming, J.E. & Shaikh, T.H. (2015). Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development. Hum. Mol. Genet. 24, 4443–53.CrossRefGoogle ScholarPubMed
Vassena, R., Han, Z., Gao, S., Baldwin, D.A., Schultz, R.M. & Latham, K.E. (2007). Tough beginnings: alterations in the transcriptome of cloned embryos during the first two cell cycles. Dev. Biol. 304, 7589.CrossRefGoogle ScholarPubMed
Welstead, G.G., Creyghton, M.P., Bilodeau, S., Cheng, A.W., Markoulaki, S., Young, R.A. & Jaenisch, R. (2012). X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc. Natl. Acad. Sci. USA 109, 13004–9.CrossRefGoogle Scholar
Yuan, X., Kong, J., Ma, Z., Li, N., Jia, R., Liu, Y., Zhou, F., Zhan, Q., Liu, G. & Gao, S. (2016). Corrigendum to ‘KDM4C, a H3K9me3 histone demethylase, is involved in the maintenance of human ESCC-initiating cells by epigenetically enhancing SOX2 expression’ [Neoplasia 18 (2016). 594–609]. Neoplasia 18, 810.CrossRefGoogle Scholar
Zhang, B., Zheng, H., Huang, B., Li, W., Xiang, Y., Peng, X., Ming, J., Wu, X., Zhang, Y., Xu, Q., Liu, W., Kou, X., Zhao, Y., He, W., Li, C., Chen, B., Li, Y., Wang, Q., Ma, J., Yin, Q., Kee, K., Meng, A., Gao, S., Xu, F., Na, J. & Xie, W. (2016). Allelic reprogramming of the histone modification H3K4me3 in early mammalian development. Nature 537, 553–7.CrossRefGoogle ScholarPubMed
Zhang, J., Ji, F., Liu, Y., Lei, X., Li, H., Ji, G., Yuan, Z. & Jiao, J. (2014). Ezh2 regulates adult hippocampal neurogenesis and memory. J. Neurosci. 34, 5184–99.CrossRefGoogle ScholarPubMed
Zhao, Q., Wu, Y., Shan, Z., Bai, G., Wang, Z., Hu, J., Liu, L., Li, T., Shen, J. & Lei, L. (2016). Serum starvation-induced cell cycle synchronization stimulated mouse rDNA transcription reactivation during somatic cell reprogramming into iPSCs. Stem Cell Res. Ther. 7, 112.CrossRefGoogle ScholarPubMed
Zheng, Z.J.J., Bou, G, Hu, LL, Wang, ZD, Shen, XH, Shan, ZY, Shen, JL, Liu, ZH, Lei, L. (2012). rRNA genes are not fully activated in mouse somatic cell nuclear transfer embryos. J. Biol. Chem. 287, 19949–60.CrossRefGoogle Scholar

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