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. 2016 Apr 22;15(3):618–628. doi: 10.1016/S2095-3119(15)61100-5

Methylation profile of bovine Oct4 gene coding region in relation to three germ layers

Xin-yu ZHOU a,*, Liang-liang LIU b,*, Wen-chao JIA c, Chuan-ying PAN a,c,*
PMCID: PMC7128269  PMID: 32288951

Abstract

Previous studies have shown that octamer-binding transcription factor 4 (Oct4) plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage differentiation which are regulated by DNA methylation. To explore the relationship between the methylation pattern of Oct4 gene exon 1 and embryonic development, in this work, five different tissues (heart, liver, lung, cerebrum and cerebellum) from three germ layers were chosen from low age (50–60 d) and advanced age (60–70 d) of fetal cattle and the differences between tissues or ages were analyzed, respectively. The result showed that the DNA methylation level of Oct4 gene exon 1 was significant different (P<0.01) between any two of three germ layers in low age (<60 d), but kept steady of advanced age (P>0.05) (>60 d), suggesting that 60-d post coital was an important boundary for embryonic development. In addition, in ectoderm (cerebrum and cerebellum), there was no significant methylation difference of Oct4 gene exon 1 between low age and advanced age (P>0.05), but the result of endoderm (liver and lung) and mesoderm (heart) were on the contrary (P<0.01), which indicated the development of ectoderm was earlier than endoderm and mesoderm. The methylation differences from the 3rd, 5th and 9th CpG-dinucleotide loci of Oct4 gene exon 1 were significantly different between each two of three germ layers (P<0.05), indicating that these three loci may have important influence on bovine embryonic development. This study showed that bovine germ layers differentiation was significantly related to the DNA methylation status of Oct4 gene exon 1. This work firstly identified the DNA methylation profile of bovine Oct4 gene exon 1 and its association with germ layers development in fetus and adult of cattle. Moreover, the work also provided epigenetic information for further studying bovine embryonic development and cellular reprogramming.

Keywords: bovine, DNA methylation, octamer-binding transcription factor 4 (Oct4), exon, germ layer

Contributor Information

Xin-yu ZHOU, Email: zhouxinyu0531@163.com.

Liang-liang LIU, Email: lingyun79626@126.com.

Chuan-ying PAN, Email: panyu1980@126.com.

References

  1. Al-Khtib M, Blachère T, Guérin J F, Lefèvre A. Methylation profile of the promoters of Nanog and Oct4 in ICSI human embryos. Human Reproduction. 2012;27:2948–2954. doi: 10.1093/humrep/des284. [DOI] [PubMed] [Google Scholar]
  2. Basu A, Dasari V, Mishra R K, Khosla S. The CpG island encompassing the promoter and first exon of human DNMT3L gene is a PcG/TrX response element (PRE) PLOS ONE. 2014;9:e93561. doi: 10.1371/journal.pone.0093561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beltrami A P, Cesselli D, Bergamin N, Marcon P, Rigo S, Puppato E, D'Aurizio F, Verardo R, Piazza S, Pignatelli A, Poz A, Baccarani U, Damiani D, Fanin R, Mariuzzi L, Finato N, Masolini P, Burelli S, Belluzzi O, Schneider C. Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow) Blood. 2007;110:3438–3446. doi: 10.1182/blood-2006-11-055566. [DOI] [PubMed] [Google Scholar]
  4. Brenet F, Moh M, Funk P, Feierstein E, Viale A J, Socci N D, Scandura J M. DNA methylation of the first exon is tightly linked to transcriptional silencing. PLoS ONE. 2011;6:e14524. doi: 10.1371/journal.pone.0014524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buganim Y, Faddah D A, Cheng A W, Itskovich E, Markoulaki S, Ganz K, Klemm S L, van Oudenaarden A, Jaenisch R. Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell. 2012;150:1209–1222. doi: 10.1016/j.cell.2012.08.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chaumeil J, Skok J A. The role of CTCF in regulating V(D)J recombination. Current Opinion in Immunology. 2012;24:153–159. doi: 10.1016/j.coi.2012.01.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Choy M K, Movassagh M, Goh H G, Bennett M R, Down T A, Foo R S. Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated. BMC Genomics. 2010;11:519. doi: 10.1186/1471-2164-11-519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Corry G N, Tanasijevic B, Barry E R, Krueger W, Rasmussen T P. Rasmussen epigenetic regulatory mechanisms during pre-implantation development. Birth Defects Research (Part C: Embryo Today: Reviews) 2009;87:297–313. doi: 10.1002/bdrc.20165. [DOI] [PubMed] [Google Scholar]
  9. Davis S F, Hood J, Thomas A, Bunnell B A. Isolation of adult rhesus neural stem and progenitor cells and differentiation into immature oligodendrocytes. Stem Cells and Development. 2006;15:191–199. doi: 10.1089/scd.2006.15.191. [DOI] [PubMed] [Google Scholar]
  10. Van Dyck F, Declercq J, Braem C V, Van de Ven W J. PLAG1, the prototype of the PLAG gene family: Versatility in tumour development. International Journal of Oncology. 2007;30:765–774. [PubMed] [Google Scholar]
  11. Goissis M D, Cibelli J B. Functional characterization of SOX2 in bovine preimplantation embryos. Biology of Reproduction. 2014;90:30. doi: 10.1095/biolreprod.113.111526. [DOI] [PubMed] [Google Scholar]
  12. Harvey E B. Aging and foetal development. In: Cole H H, Eupps P T, editors. Reproduction in Domestic Animals. Academic Press; New York, America: 1959. pp. 461–466. [Google Scholar]
  13. Hawkins K, Joy S, McKay T. Cell signalling pathways underlying induced pluripotent stem cell reprogramming. World Journal of Stem Cells. 2014;6:620–628. doi: 10.4252/wjsc.v6.i5.620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hernández-Negrete I, Sala-Newby G B, Perl A, Kunkel G R, Newby A C, Bond M. Adhesion-dependent Skp2 transcription requires selenocysteine tRNA gene transcription-activating factor (STAF) The Biochemical Journal. 2011;436:133–143. doi: 10.1042/BJ20101798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Herreros-Villanueva M, Bujanda L, Billadeau D D, Zhang J S. Embryonic stem cell factors and pancreatic cancer. World Journal of Gastroenterology. 2014;20:2247–2255. doi: 10.3748/wjg.v20.i9.2247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hilger-Eversheim K, Moser M, Schorle H, Buettner R. Regulatory roles of AP-2 transcription factors in vertebrate development, apoptosis and cell-cycle control. Gene. 2000;260:1–12. doi: 10.1016/s0378-1119(00)00454-6. [DOI] [PubMed] [Google Scholar]
  17. Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science. 2013;341:651–654. doi: 10.1126/science.1239278. [DOI] [PubMed] [Google Scholar]
  18. Illingworth R S, Bird A P. CpG islands – ‘a rough guide‚. FEBS Letters. 2009;583:1713–1720. doi: 10.1016/j.febslet.2009.04.012. [DOI] [PubMed] [Google Scholar]
  19. Jerabek S, Merino F, Schöler H R, Cojocaru V. OCT4: Dynamic DNA binding pioneers stem cell pluripotency. Biochimica et Biophysica Acta. 2014;1839:138–154. doi: 10.1016/j.bbagrm.2013.10.001. [DOI] [PubMed] [Google Scholar]
  20. Kelly V P, Suzuki T, Nakajima O, Arai T, Tamai Y, Takahashi S, Nishimura S, Yamamoto M. The distal sequence element of the selenocysteine tRNA gene is a tissue-dependent enhancer essential for mouse embryogenesis. Molecular and Cellular Biology. 2005;25:3658–3669. doi: 10.1128/MCB.25.9.3658-3669.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kim J, Chu J, Shen X, Wang J, Orkin S H. An extended transcriptional network for pluripotency of embryonic stem cells. Cell. 2008;132:1049–1061. doi: 10.1016/j.cell.2008.02.039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kumar D, Talluri T R, Anand T, Kues W A. Induced pluripotent stem cells: Mechanisms, achievements and perspectives in farm animals. World Journal of Stem Cells. 2015;7:315–328. doi: 10.4252/wjsc.v7.i2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Li J Y, Pu M T, Hirasawa R, Li B Z, Huang Y N, Zeng R, Jing N H, Chen T, Li E, Sasaki H, Xu G L. Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog. Molecular and Cellular Biology. 2007;27:8748–8759. doi: 10.1128/MCB.01380-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Li L C, Dahiya R. MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002;18:1427–1431. doi: 10.1093/bioinformatics/18.11.1427. [DOI] [PubMed] [Google Scholar]
  25. Ling T Y, Kuo M D, Li C L, Yu A L, Huang Y H, Wu T J, Lin Y C, Chen S H, Yu J. Identification of pulmonary Oct-4+ stem/progenitor cells and demonstration of their susceptibility to SARS coronavirus (SARS-CoV) infection in vitro. Proceedings of the National Academy of Sciences of the United States America. 2006;103:9530–9535. doi: 10.1073/pnas.0510232103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Liu K, Song Y, Yu H, Zhao T. Understanding the roadmaps to induced pluripotency. Cell Death & Disease. 2014;5:e1232. doi: 10.1038/cddis.2014.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Loh Y H, Wu Q, Chew J L, Vega V B, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong K Y, Sung K W, Lee C W, Zhao X D, Chiu K P, Lipovich L, Kuznetsov V A, Robson P, Stanton L W, Wei C L, et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genetics, 38, 431–440. [DOI] [PubMed]
  28. Masui S, Nakatake Y, Toyooka Y, Shimosato D, Yagi R, Takahashi K, Okochi H, Okuda A, Matoba R, Sharov A A, Ko M S, Niwa H. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nature Cell Biology. 2007;9:625–635. doi: 10.1038/ncb1589. [DOI] [PubMed] [Google Scholar]
  29. Moser M, Imhof A, Pscherer A, Bauer R, Amselgruber W, Sinowatz F, Hofstädter F, Schüle R, Buettner R. Cloning and characterization of a second AP-2 transcription factor: AP-2 beta. Development. 1995;121:2779–2788. doi: 10.1242/dev.121.9.2779. [DOI] [PubMed] [Google Scholar]
  30. Nei M, Li W H. Mathematical model for studying genetic variation in terms of restriction endonucleases. Proceedings of the National Academy of Sciences of the United States of America. 1979;76:5269–5273. doi: 10.1073/pnas.76.10.5269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Okuda T, Tagawa K, Qi M L, Hoshio M, Ueda H, Kawano H, Kanazawa I, Muramatsu M, Okazawa H. Oct-3/4 repression accelerates differentiation of neural progenitor cells in vitro and in vivo. Brain Research. Molecular Brain Research. 2004;132:18–30. doi: 10.1016/j.molbrainres.2004.08.021. [DOI] [PubMed] [Google Scholar]
  32. Palmieri S L, Peter W, Hess H, Schöler H R. Oct-4 transcription factor is differentially expressed in the mouse embryo during establishment of the first two extraembryonic cell lineages involved in implantation. Developmental Biology. 1994;166:259–267. doi: 10.1006/dbio.1994.1312. [DOI] [PubMed] [Google Scholar]
  33. Pan C, Jia W, Wu X, Zhao H, Liu S, Lei C, Lan X, Chen H. DNA methylation profile of DNA methyltransferase 3b (Dnmt3b) gene and its influence on growth traits in goat. The Journal of Animal and Plant Sciences. 2013;23:380–387. [Google Scholar]
  34. Park I H, Zhao R, West J A, Yabuuchi A, Huo H, Ince T A, Lerou P H, Lensch M W, Daley G Q. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008;451:141–146. doi: 10.1038/nature06534. [DOI] [PubMed] [Google Scholar]
  35. Qin C H, Chu Q, Chu G Y, Zhang Y, Zhang Q, Zhang S L, Sun D X. Mapping QTLs affecting economic traits on BTA3 in Chinese holstein with microsatellite markers. Journal of Integrative Agriculture. 2014;13:1999–2004. [Google Scholar]
  36. Robertson K D, Wolffe A P. DNA methylation in health and disease. Nature Reviews Genetics. 2000;1:11–19. doi: 10.1038/35049533. [DOI] [PubMed] [Google Scholar]
  37. Rosner M H, Vigano M A, Ozato K, Timmons P M, Poirier F, Rigby P W, Staudt L M. A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature. 1990;345:686–692. doi: 10.1038/345686a0. [DOI] [PubMed] [Google Scholar]
  38. Sagrinati C, Netti G S, Mazzinghi B, Lazzeri E, Liotta F, Frosali F, Ronconi E, Meini C, Gacci M, Squecco R, Carini M, Gesualdo L, Francini F, Maggi E, Annunziato F, Lasagni L, Serio M, Romagnani S, Romagnani P. Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys. Journal of American Society of Nephrology. 2006;17:2443–2456. doi: 10.1681/ASN.2006010089. [DOI] [PubMed] [Google Scholar]
  39. Santos F, Hendrich B, Reik W, Dean W. Dynamic reprogramming of DNA methylation in the early mouse embryo. Developmental Biology. 2002;241:172–182. doi: 10.1006/dbio.2001.0501. [DOI] [PubMed] [Google Scholar]
  40. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676. doi: 10.1016/j.cell.2006.07.024. [DOI] [PubMed] [Google Scholar]
  41. Thomas T, Nowka K, Lan L, Derwahl M. Expression of endoderm stem cell markers: evidence for the presence of adult stem cells in human thyroid glands. Thyroid. 2006;16:537–544. doi: 10.1089/thy.2006.16.537. [DOI] [PubMed] [Google Scholar]
  42. Wang H, Maurano M T, Qu H, Varley K E, Gertz J, Pauli F, Lee K, Canfield T, Weaver M, Sandstrom R, Thurman R E, Kaul R, Myers R M, Stamatoyannopoulos J A. Widespread plasticity in CTCF occupancy linked to DNA methylation. Genome Research. 2012;22:1680–1688. doi: 10.1101/gr.136101.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wei Z, Yang Y, Zhang P, Andrianakos R, Hasegawa K, Lyu J, Chen X, Bai G, Liu C, Pera M, Lu W. Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells. 2009;27:2969–2978. doi: 10.1002/stem.231. [DOI] [PubMed] [Google Scholar]
  44. Werling U, Schorle H. Transcription factor gene AP-2γ essential for early murine development. Molecular and Cellular Biology. 2002;22:3149–3156. doi: 10.1128/MCB.22.9.3149-3156.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. West-Mays J A, Coyle B M, Piatigorsky J, Papagiotas S, Libby D. Ectopic expression of AP-2α transcription factor in the lens disrupts fiber cell differentiation. Developmental Biology. 2002;245:13–27. doi: 10.1006/dbio.2002.0624. [DOI] [PubMed] [Google Scholar]
  46. Winters L M, Green W W, Comstock R E. Prenatal development of the bovine. University of Minnesota, Agricultural Experiment Stationy. 1942;151:1–50. [Google Scholar]
  47. Wu G, Schöler H R. Role of Oct4 in the early embryo development. Cell Regeneration (London, England) 2014:3–7. doi: 10.1186/2045-9769-3-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Xu W H, Li Z C, Ouyang Z P, Yu B, Shi J S, Liu D W, Wu Z F. RNA-Seq transcriptome analysis of porcine cloned and in vitro fertilized blastocysts. Journal of Integrative Agriculture. 2015;14:926–938. [Google Scholar]
  49. Yamazaki Y, Fujita T C, Low E W, Alarcón V B, Yanagimachi R, Marikawa Y. Gradual DNA demethylation of the Oct4 promoter in cloned mouse embryos. Molecular Reproduction and Development. 2006;73:180–188. doi: 10.1002/mrd.20411. [DOI] [PubMed] [Google Scholar]
  50. Yeom Y I, Fuhrmann G, Ovitt C E, Brehm A, Ohbo K, Gross M, Hubner K, Scholer H R. Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells. Development. 1996;122:881–894. doi: 10.1242/dev.122.3.881. [DOI] [PubMed] [Google Scholar]
  51. Yu J, Vodyanik M A, Smuga-Otto K, Antosiewicz-Bourget J, Frane J L, Tian S, Nie J, Jonsdottir G A, Ruotti V, Stewart R, Slukvin I I, Thomson J A. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–1920. doi: 10.1126/science.1151526. [DOI] [PubMed] [Google Scholar]
  52. Zhang H J, Siu M K, Wong E S, Wong K Y, Li A S, Chan K Y, Ngan H Y, Cheung A N. Oct4 is epigenetically regulated by methylation in normal placenta and gestational trophoblastic disease. Placenta. 2008;29:549–554. doi: 10.1016/j.placenta.2008.03.003. [DOI] [PubMed] [Google Scholar]

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