본문 바로가기
KERD
논문KCI 등재

Imprinted gene Zinc finger protein 127 is a novel regulator of master pluripotency transcription factor, Oct4

0

조회

0

다운로드

2

인용

0

참고문헌

키워드

주제분류화학

초록

Induced pluripotent stem cells (iPSCs) show great promise for replacing current stem cell therapies in the field of regenerative medicine. However, the original method for cellular reprogramming, involving four exogenous transcription factors, is characterized by low efficiency. Here, we focused on using epigenetic modifications to enhance the reprogramming efficiency. We hypothesized that there would be a new reprogramming factor involved in DNA demethylation, acting on the promoters of pluripotency-related genes. We screened proteins that bind to the methylated promoter of Oct4 and identified Zinc finger protein 127 (Zfp127), the functions of which have not yet been identified. We found that Zfp127 binds to the Oct4 promoter. Overexpression of Zfp127 in fibroblasts induced demethylation of the Oct4 promoter, thus enhancing Oct4 promoter activity and gene expression. These results demonstrate that Zfp127 is a novel regulator of Oct4, and may become a potent target to improve cellular reprogramming.

Abstract

Induced pluripotent stem cells (iPSCs) show great promise for replacing current stem cell therapies in the field of regenerative medicine. However, the original method for cellular reprogramming, involving four exogenous transcription factors, is characterized by low efficiency. Here, we focused on using epigenetic modifications to enhance the reprogramming efficiency. We hypothesized that there would be a new reprogramming factor involved in DNA demethylation, acting on the promoters of pluripotency-related genes. We screened proteins that bind to the methylated promoter of Oct4 and identified Zinc finger protein 127 (Zfp127), the functions of which have not yet been identified. We found that Zfp127 binds to the Oct4 promoter. Overexpression of Zfp127 in fibroblasts induced demethylation of the Oct4 promoter, thus enhancing Oct4 promoter activity and gene expression. These results demonstrate that Zfp127 is a novel regulator of Oct4, and may become a potent target to improve cellular reprogramming.

참고문헌 (30)

  1. Takahashi K, "Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors", Cell, 126, pp.663~676 (2006)[DOI]
  2. Okita K, "Generation of mouse induced pluripotent stem cells without viral vectors", Science, 322, pp.949~953 (2008)[DOI]
  3. Zhou W, "Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells", Stem Cells, 27, pp.2667~2674 (2009)[DOI]
  4. Miyoshi N, "Reprogramming of mouse and human cells to pluripotency using mature microRNAs", Cell Stem Cell, 8, pp.633~638 (2011)[DOI]
  5. Xu N, "MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells", Cell, 137, pp.647~658 (2009)[DOI]
  6. Cho HJ, "Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation", Blood, 116, pp.386~395 (2010)[DOI]
  7. Kim D, "Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins", Cell Stem Cell, 4, pp.472~476 (2009)[DOI]
  8. Yu J, "Induced pluripotent stem cell lines derived from human somatic cells", Science, 318, pp.1917~1920 (2007)[DOI]
  9. Sridharan R, "Role of the murine reprogramming factors in the induction of pluripotency", Cell, 136, pp.364~377 (2009)[DOI]
  10. Zhao Y, "Two supporting factors greatly improve the efficiency of human iPSC generation", Cell Stem Cell, 3, pp.475~479 (2008)[DOI]
  11. Silva J, "Nanog is the gateway to the pluripotent ground state", Cell, 138, pp.722~737 (2009)[DOI]
  12. Hanna J, "Direct cell reprogramming is a stochastic process amenable to acceleration", Nature, 462, pp.595~601 (2009)[DOI]
  13. Buganim Y, "Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase", Cell, 150, pp.1209~1222 (2012)[DOI]
  14. Eminli S, "Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells", Nat Genet, 41, pp.968~976 (2009)[DOI]
  15. 신지훈, "Oct4 resetting by Aurkb–PP1 cell cycle axis determines the identity of mouse embryonic stem cells", BMB Reports, 49(10), pp.527~528 (2016), 생화학분자생물학회
  16. Freberg CT, "Epigenetic reprogramming of OCT4 and NANOG regulatory regions by embryonal carcinoma cell extract", Mol Biol Cell, 18, pp.1543~1553 (2007)[DOI]
  17. Hochedlinger K, "Epigenetic reprogramming and induced pluripotency", Development, 136, pp.509~523 (2009)[DOI]
  18. Bhutani N, "Reprogramming towards pluripotency requires AID-dependent DNA demethylation", Nature, 463, pp.1042~1047 (2010)[DOI]
  19. Jong MT, "Imprinting of a RING zinc-finger encoding gene in the mouse chromosome region homologous to the Prader-Willi syndrome genetic region", Hum Mol Genet, 8, pp.795~803 (1999)[DOI]
  20. Kwon YW, "Role of Zscan4 in secondary murine iPSC derivation mediated by protein extracts of ESC or iPSC", Biomaterials, 59, pp.102~115 (2015)[DOI]
  21. Imamura M, "Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells", BMC Dev Biol, 6, pp.34~ (2006)[DOI]
  22. Okita K, "Generation of germline-competent induced pluripotent stem cells", Nature, 448, pp.313~317 (2007)[DOI]
  23. Gu P, "Differential recruitment of methyl CpG-binding domain factors and DNA methyltransferases by the orphan receptor germ cell nuclear factor initiates the repression and silencing of Oct4", Stem Cells, 29, pp.1041~1051 (2011)[DOI]
  24. Jin SG, "GADD45A does not promote DNA demethylation", PLoS Genet, 4, pp.e1000013~ (2008)[DOI]
  25. Sharov AA, "Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data", BMC Genomics, 9, pp.269~ (2008)[DOI]
  26. 이정은, "An efficient SCNT technology for the establishment of personalized and public human pluripotent stem cell banks", BMB Reports, 49(4), pp.197~198 (2016), 생화학분자생물학회
  27. Jong MT, "A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region", Hum Mol Genet, 8, pp.783~793 (1999)[DOI]
  28. Hill PW, "DNA demethylation, Tet proteins and 5-hydroxymethylcytosine in epigenetic reprogramming: an emerging complex story", Genomics, 104, pp.324~333 (2014)[DOI]
  29. Cha MY, "Protein-induced pluripotent stem cells ameliorate cognitive dysfunction and Reduce Abeta deposition in a mouse model of alzheimer's disease", Stem Cells Transl Med, 6, pp.293~305 (2016)
  30. Hattori N, "Epigenetic control of mouse Oct-4 gene expression in embryonic stem cells and trophoblast stem cells", J Biol Chem, 279, pp.17063~17069 (2004)[DOI]

이 간행물의 다른 논문 (9건)