Effects of ten–eleven translocation 1 (Tet1) on DNA methylation and gene expression in chicken primordial germ cells
Minli Yu
A B , Dongfeng Li A , Wanyan Cao A , Xiaolu Chen A and Wenxing Du A B
+ Author Affiliations
- Author Affiliations
A Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095 Jiangsu Province, PR China.
B Corresponding authors. Emails: yuminli@njau.edu.cn; duwx@njau.edu.cn
Reproduction, Fertility and Development 31(3) 509-520 https://doi.org/10.1071/RD18145
Abstract
Ten–eleven translocation 1 (Tet1) is involved in DNA demethylation in primordial germ cells (PGCs); however, the precise regulatory mechanism remains unclear. In the present study the dynamics of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in developing PGCs and the role of Tet1 in PGC demethylation were analysed. Results show that 5mC levels dropped significantly after embryonic Day 4 (E4) and 5hmC levels increased reaching a peak at E5–E5.5. Interestingly, TET1 protein was highly expressed during E5 to E5.5, which showed a consistent trend with 5hmC. The expression of pluripotency-associated genes (Nanog, PouV and SRY-box 2 (Sox2)) and germ cell-specific genes (caveolin 1 (Cav1), piwi-like RNA-mediated gene silencing 1 (Piwi1) and deleted in azoospermia-like (Dazl)) was upregulated after E5, whereas the expression of genes from the DNA methyltransferase family was decreased. Moreover, the Dazl gene was highly methylated in early PGCs and then gradually hypomethylated. Knockdown of Tet1 showed impaired survival and proliferation of PGCs, as well as increased 5mC levels and reduced 5hmC levels. Further analysis showed that knockdown of Tet1 led to elevated DNA methylation levels of Dazl and downregulated gene expression including Dazl. Thus, this study reveals the dynamic epigenetic reprogramming of chicken PGCs in vivo and the molecular mechanism of Tet1 in regulating genomic DNA demethylation and hypomethylation of Dazl during PGC development.
Additional keywords: Dazl, DNA demethylation, dynamics, 5-hydroxymethylcytosine.
References
Bagci, H., and Fisher, A. G. (2013). DNA demethylation in pluripotency and reprogramming: the role of Tet proteins and cell division. Cell Stem Cell 13, 265–269.| DNA demethylation in pluripotency and reprogramming: the role of Tet proteins and cell division.Crossref | GoogleScholarGoogle Scholar |
Blaschke, K., Ebata, K. T., Karimi, M. M., Zepeda-Martinez, J. A., Goyal, P., Mahapatra, S., Tam, A., Laird, D. J., Hirst, M., Rao, A., Lorincz, M. C., and Ramalho-Santos, M. (2013). Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature 500, 222–226.
| Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.Crossref | GoogleScholarGoogle Scholar |
Brons, I. G., Smithers, L. E., Trotter, M. W., Rugg-Gunn, P., Sun, B., Chuva de Sousa Lopes, S. M., Howlett, S. K., Clarkson, A., Ahrlund-Richter, L., Pedersen, R. A., and Vallier, L. (2007). Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191–195.
| Derivation of pluripotent epiblast stem cells from mammalian embryos.Crossref | GoogleScholarGoogle Scholar |
Costa, Y., Ding, J. J., Theunissen, T. W., Faiola, F., Hore, T. A., Shliaha, P. V., Fidalgo, M., Saunders, A., Lawrence, M., Dietmann, S., Das, S., Levasseur, D. N., Li, Z., Xu, M. J., Reik, W., Silva, J. C. R., and Wang, J. L. (2013). NANOG-dependent function of TET1 and TET2 in establishment of pluripotency. Nature 495, 370–374.
| NANOG-dependent function of TET1 and TET2 in establishment of pluripotency.Crossref | GoogleScholarGoogle Scholar |
Dawlaty, M. M., Breiling, A., Le, T., Barrasa, M. I., Raddatz, G., Gao, Q., Powell, B. E., Cheng, A. W., Faull, K. F., Lyko, F., and Jaenisch, R. (2014). Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev. Cell 29, 102–111.
| Loss of Tet enzymes compromises proper differentiation of embryonic stem cells.Crossref | GoogleScholarGoogle Scholar |
Ficz, G., Branco, M. R., Seisenberger, S., Santos, F., Krueger, F., Hore, T. A., Marques, C. J., Andrews, S., and Reik, W. (2011). Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473, 398–402.
| Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation.Crossref | GoogleScholarGoogle Scholar |
Gao, Y., Chen, J., Li, K., Wu, T., Huang, B., Liu, W., Kou, X., Zhang, Y., Huang, H., Jiang, Y., Yao, C., Liu, X., Lu, Z., Xu, Z., Kang, L., Wang, H., Cai, T., and Gao, S. (2013). Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming. Cell Stem Cell 12, 453–469.
| Replacement of Oct4 by Tet1 during iPSC induction reveals an important role of DNA methylation and hydroxymethylation in reprogramming.Crossref | GoogleScholarGoogle Scholar |
Guibert, S., Forne, T., and Weber, M. (2012). Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome Res. 22, 633–641.
| Global profiling of DNA methylation erasure in mouse primordial germ cells.Crossref | GoogleScholarGoogle Scholar |
Hargan-Calvopina, J., Taylor, S., Cook, H., Hu, Z. X., Lee, S. A., Yen, M. R., Chiang, Y. S., Chen, P. Y., and Clark, A. T. (2016). Stage-specific demethylation in primordial germ cells safeguards against precocious differentiation. Dev. Cell 39, 75–86.
| Stage-specific demethylation in primordial germ cells safeguards against precocious differentiation.Crossref | GoogleScholarGoogle Scholar |
Hashimoto, H., Liu, Y., Upadhyay, A. K., Chang, Y., Howerton, S. B., Vertino, P. M., Zhang, X., and Cheng, X. (2012). Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation. Nucleic Acids Res. 40, 4841–4849.
| Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation.Crossref | GoogleScholarGoogle Scholar |
He, S., Sun, H., Lin, L., Zhang, Y., Chen, J., Liang, L., Li, Y., Zhang, M., Yang, X., Wang, X., Wang, F., Zhu, F., Pei, D., and Zheng, H. (2017). Passive DNA demethylation preferentially up-regulates pluripotency-related genes and facilitates the generation of induced pluripotent stem cells. J. Biol. Chem. 292, 18542–18555.
| Passive DNA demethylation preferentially up-regulates pluripotency-related genes and facilitates the generation of induced pluripotent stem cells.Crossref | GoogleScholarGoogle Scholar |
Ito, S., D’Alessio, A. C., Taranova, O. V., Hong, K., Sowers, L. C., and Zhang, Y. (2010). Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466, 1129–1133.
| Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.Crossref | GoogleScholarGoogle Scholar |
Kagiwada, S., Kurimoto, K., Hirota, T., Yamaji, M., and Saitou, M. (2013). Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice. EMBO J. 32, 340–353.
| Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice.Crossref | GoogleScholarGoogle Scholar |
Khoueiry, R., Sohni, A., Thienpont, B., Luo, X. L., Velde, J. V., Bartoccetti, M., Boeckx, B., Zwijsen, A., Rao, A., Lambrechts, D., and Koh, K. P. (2017). Lineage-specific functions of TET1 in the postimplantation mouse embryo. Nat. Genet. 49, 1061–1072.
| Lineage-specific functions of TET1 in the postimplantation mouse embryo.Crossref | GoogleScholarGoogle Scholar |
Kito, G., Aramaki, S., Tanaka, K., Soh, T., Yamauchi, N., and Hattori, M. A. (2010). Temporal and spatial differential expression of chicken germline-specific proteins cDAZL, CDH and CVH during gametogenesis. J. Reprod. Dev. 56, 341–346.
| Temporal and spatial differential expression of chicken germline-specific proteins cDAZL, CDH and CVH during gametogenesis.Crossref | GoogleScholarGoogle Scholar |
Kohli, R. M., and Zhang, Y. (2013). TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502, 472–479.
| TET enzymes, TDG and the dynamics of DNA demethylation.Crossref | GoogleScholarGoogle Scholar |
Liao, J., Karnik, R., Gu, H., Ziller, M. J., Clement, K., Tsankov, A. M., Akopian, V., Gifford, C. A., Donaghey, J., Galonska, C., Pop, R., Reyon, D., Tsai, S. Q., Mallard, W., Joung, J. K., Rinn, J. L., Gnirke, A., and Meissner, A. (2015). Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Nat. Genet. 47, 469–478.
| Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells.Crossref | GoogleScholarGoogle Scholar |
Lin, Y., and Page, D. C. (2005). Dazl deficiency leads to embryonic arrest of germ cell development in XY C57BL/6 mice. Dev. Biol. 288, 309–316.
| Dazl deficiency leads to embryonic arrest of germ cell development in XY C57BL/6 mice.Crossref | GoogleScholarGoogle Scholar |
Nakamura, Y., Yamamoto, Y., Usui, F., Ono, T., Takeda, K., Nirasawa, K., Kagami, H., and Tagami, T. (2007). The distribution pattern of primordial germ cells in early chick embryos. Reprod. Fertil. Dev. 19, 192–193.
| The distribution pattern of primordial germ cells in early chick embryos.Crossref | GoogleScholarGoogle Scholar |
Navarro-Costa, P., Nogueira, P., Carvalho, M., Leal, F., Cordeiro, I., Calhaz-Jorge, C., Goncalves, J., and Plancha, C. E. (2010). Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm. Hum. Reprod. 25, 2647–2654.
| Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm.Crossref | GoogleScholarGoogle Scholar |
Onyango, P., Jiang, S., Uejima, H., Shamblott, M. J., Gearhart, J. D., Cui, H., and Feinberg, A. P. (2002). Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages. Proc. Natl. Acad. Sci. USA 99, 10599–10604.
| Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages.Crossref | GoogleScholarGoogle Scholar |
Saitou, M., Barton, S. C., and Surani, M. A. (2002). A molecular programme for the specification of germ cell fate in mice. Nature 418, 293–300.
| A molecular programme for the specification of germ cell fate in mice.Crossref | GoogleScholarGoogle Scholar |
Saunders, P. T., Turner, J. M., Ruggiu, M., Taggart, M., Burgoyne, P. S., Elliott, D., and Cooke, H. J. (2003). Absence of mDazl produces a final block on germ cell development at meiosis. Reproduction 126, 589–597.
| Absence of mDazl produces a final block on germ cell development at meiosis.Crossref | GoogleScholarGoogle Scholar |
Seisenberger, S., Andrews, S., Krueger, F., Arand, J., Walter, J., Santos, F., Popp, C., Thienpont, B., Dean, W., and Reik, W. (2012). The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol. Cell 48, 849–862.
| The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells.Crossref | GoogleScholarGoogle Scholar |
Smith, Z. D., and Meissner, A. (2013). DNA methylation: roles in mammalian development. Nat. Rev. Genet. 14, 204–220.
| DNA methylation: roles in mammalian development.Crossref | GoogleScholarGoogle Scholar |
Tsunekawa, N., Naito, M., Sakai, Y., Nishida, T., and Noce, T. (2000). Isolation of chicken vasa homolog gene and tracing the origin of primordial germ cells. Development 127, 2741–2750.
Uysal, F., Ozturk, S., and Akkoyunlu, G. (2017). DNMT1, DNMT3A and DNMT3B proteins are differently expressed in mouse oocytes and early embryos. J. Mol. Histol. 48, 417–426.
| DNMT1, DNMT3A and DNMT3B proteins are differently expressed in mouse oocytes and early embryos.Crossref | GoogleScholarGoogle Scholar |
Vincent, J. J., Huang, Y., Chen, P. Y., Feng, S., Calvopina, J. H., Nee, K., Lee, S. A., Le, T., Yoon, A. J., Faull, K., Fan, G., Rao, A., Jacobsen, S. E., Pellegrini, M., and Clark, A. T. (2013). Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells. Cell Stem Cell 12, 470–478.
| Stage-specific roles for tet1 and tet2 in DNA demethylation in primordial germ cells.Crossref | GoogleScholarGoogle Scholar |
Yamamoto, Y., Usui, F., Nakamura, Y., Ito, Y., Tagami, T., Nirasawa, K., Matsubara, Y., Ono, T., and Kagami, H. (2007). A novel method to isolate primordial germ cells and its use for the generation of germline chimeras in chicken. Biol. Reprod. 77, 115–119.
| A novel method to isolate primordial germ cells and its use for the generation of germline chimeras in chicken.Crossref | GoogleScholarGoogle Scholar |
Yu, M., Ge, C., Zeng, W., Mi, Y., and Zhang, C. (2012). Retinoic acid promotes proliferation of chicken primordial germ cells via activation of PI3K/Akt-mediated NF-kappaB signalling cascade. Cell Biol. Int. 36, 705–712.
| Retinoic acid promotes proliferation of chicken primordial germ cells via activation of PI3K/Akt-mediated NF-kappaB signalling cascade.Crossref | GoogleScholarGoogle Scholar |
Yu, M., Xu, Y., Yu, D., and Du, W. (2015). Comparative analysis of temporal gene expression patterns in the developing ovary of the embryonic chicken. J. Reprod. Dev. 61, 123–133.
| Comparative analysis of temporal gene expression patterns in the developing ovary of the embryonic chicken.Crossref | GoogleScholarGoogle Scholar |
