Key Features of the POU Transcription Factor Oct4 from an Evolutionary Perspective

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2021 Oct 26

PMID 34698883

Citations 7

Authors

Evgeny I Bakhmet

Alexey N Tomilin

Affiliations

Soon will be listed here.

Abstract

Oct4, a class V POU-domain protein that is encoded by the Pou5f1 gene, is thought to be a key transcription factor in the early development of mammals. This transcription factor plays indispensable roles in pluripotent stem cells as well as in the acquisition of pluripotency during somatic cell reprogramming. Oct4 has also been shown to play a role as a pioneer transcription factor during zygotic genome activation (ZGA) from zebrafish to human. However, during the past decade, several studies have brought these conclusions into question. It was clearly shown that the first steps in mouse development are not affected by the loss of Oct4. Subsequently, the role of Oct4 as a genome activator was brought into doubt. It was also found that the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) could proceed without Oct4. In this review, we summarize recent findings, reassess the role of Oct4 in reprogramming and ZGA, and point to structural features that may underlie this role. We speculate that pluripotent stem cells resemble neural stem cells more closely than previously thought. Oct4 orthologs within the POUV class hold key roles in genome activation during early development of species with late ZGA. However, in Placentalia, eutherian-specific proteins such as Dux overtake Oct4 in ZGA and endow them with the formation of an evolutionary new tissue-the placenta.

Citing Articles

Characterization of Mesenchymal and Neural Stem Cells Response to Bipolar Microsecond Electric Pulses Stimulation.

Innamorati G, Sanchez-Petidier M, Bergafora G, Codazzi C, Palma V, Camera F Int J Mol Sci. 2025; 26(1.

PMID: 39796006 PMC: 11720446. DOI: 10.3390/ijms26010147.

Establishment of a CRISPR-Based Lentiviral Activation Library for Transcription Factor Screening in Porcine Cells.

Liang Y, Yao X, Han J, Wang J, Zhang X, Zhao D Animals (Basel). 2025; 15(1.

PMID: 39794961 PMC: 11718943. DOI: 10.3390/ani15010019.

The emergence of Sox and POU transcription factors predates the origins of animal stem cells.

Gao Y, Tan D, Girbig M, Hu H, Zhou X, Xie Q Nat Commun. 2024; 15(1):9868.

PMID: 39543096 PMC: 11564870. DOI: 10.1038/s41467-024-54152-x.

Expression in Gliomas Is Dependent on Cell Metabolism.

Volnitskiy A, Shabalin K, Pantina R, Varfolomeeva E, Kovalev R, Burdakov V Curr Issues Mol Biol. 2024; 46(2):1107-1120.

PMID: 38392188 PMC: 10887564. DOI: 10.3390/cimb46020070.

Construction of hub transcription factor-microRNAs-messenger RNA regulatory network in recurrent implantation failure.

Luo J, Huang R, Xiao P, Xu A, Dong Z, Zhang L J Assist Reprod Genet. 2023; 41(1):3-13.

PMID: 37878219 PMC: 10789703. DOI: 10.1007/s10815-023-02947-0.

References

Scholer H, Hatzopoulos A, Balling R, Suzuki N, Gruss P . A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J. 1989; 8(9):2543-50. PMC: 401252. DOI: 10.1002/j.1460-2075.1989.tb08392.x. View

Rosner M, Vigano M, Ozato K, Timmons P, Poirier F, Rigby P . A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature. 1990; 345(6277):686-92. DOI: 10.1038/345686a0. View

Herr W, Sturm R, Clerc R, Corcoran L, Baltimore D, Sharp P . The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev. 1988; 2(12A):1513-6. DOI: 10.1101/gad.2.12a.1513. View

Botquin V, Hess H, Fuhrmann G, Anastassiadis C, Gross M, Vriend G . New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2. Genes Dev. 1998; 12(13):2073-90. PMC: 316977. DOI: 10.1101/gad.12.13.2073. View

Tomilin A, Remenyi A, Lins K, Bak H, Leidel S, Vriend G . Synergism with the coactivator OBF-1 (OCA-B, BOB-1) is mediated by a specific POU dimer configuration. Cell. 2001; 103(6):853-64. DOI: 10.1016/s0092-8674(00)00189-6. View

Remenyi A, Tomilin A, Pohl E, Lins K, Philippsen A, Reinbold R . Differential dimer activities of the transcription factor Oct-1 by DNA-induced interface swapping. Mol Cell. 2001; 8(3):569-80. DOI: 10.1016/s1097-2765(01)00336-7. View

Remenyi A, Lins K, Nissen L, Reinbold R, Scholer H, Wilmanns M . Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers. Genes Dev. 2003; 17(16):2048-59. PMC: 196258. DOI: 10.1101/gad.269303. View

Nichols J, Zevnik B, Anastassiadis K, Niwa H, Chambers I, Scholer H . Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998; 95(3):379-91. DOI: 10.1016/s0092-8674(00)81769-9. View

Wu G, Han D, Gong Y, Sebastiano V, Gentile L, Singhal N . Establishment of totipotency does not depend on Oct4A. Nat Cell Biol. 2013; 15(9):1089-97. PMC: 3845671. DOI: 10.1038/ncb2816. View

10.

Niwa H, Miyazaki J, Smith A . Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000; 24(4):372-6. DOI: 10.1038/74199. View

11.

Radzisheuskaya A, Chia G, Dos Santos R, Theunissen T, Castro L, Nichols J . A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages. Nat Cell Biol. 2013; 15(6):579-90. PMC: 3671976. DOI: 10.1038/ncb2742. View

12.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

13.

Velychko S, Adachi K, Kim K, Hou Y, MacCarthy C, Wu G . Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs. Cell Stem Cell. 2019; 25(6):737-753.e4. PMC: 6900749. DOI: 10.1016/j.stem.2019.10.002. View

14.

Michael A, Grand R, Isbel L, Cavadini S, Kozicka Z, Kempf G . Mechanisms of OCT4-SOX2 motif readout on nucleosomes. Science. 2020; 368(6498):1460-1465. DOI: 10.1126/science.abb0074. View

15.

Le Bin G, Munoz-Descalzo S, Kurowski A, Leitch H, Lou X, Mansfield W . Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst. Development. 2014; 141(5):1001-10. PMC: 3929414. DOI: 10.1242/dev.096875. View

16.

Frum T, Halbisen M, Wang C, Amiri H, Robson P, Ralston A . Oct4 cell-autonomously promotes primitive endoderm development in the mouse blastocyst. Dev Cell. 2013; 25(6):610-22. PMC: 4076445. DOI: 10.1016/j.devcel.2013.05.004. View

17.

Verrijzer C, van der Vliet P . POU domain transcription factors. Biochim Biophys Acta. 1993; 1173(1):1-21. DOI: 10.1016/0167-4781(93)90237-8. View

18.

Klemm J, Rould M, Aurora R, Herr W, Pabo C . Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules. Cell. 1994; 77(1):21-32. DOI: 10.1016/0092-8674(94)90231-3. View

19.

Pan G, Qin B, Liu N, Scholer H, Pei D . Identification of a nuclear localization signal in OCT4 and generation of a dominant negative mutant by its ablation. J Biol Chem. 2004; 279(35):37013-20. DOI: 10.1074/jbc.M405117200. View

20.

Kong X, Liu J, Li L, Yue L, Zhang L, Jiang H . Functional interplay between the RK motif and linker segment dictates Oct4-DNA recognition. Nucleic Acids Res. 2015; 43(9):4381-92. PMC: 4482079. DOI: 10.1093/nar/gkv323. View