Oct-4

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Oct-4
Properties of human protein
Mass / length primary structure 360 amino acids
Isoforms A, B
Identifier
Gene name POU5F1
External IDs

Oct-4 ( octamer-binding transcription factor ; Engl. Octamer binding transcription factor 4 ), also known as OCT3 , POU5F1 or MGC22487 referred to is a transcription factor of the POU family . The gene is only expressed in cells with a higher development potential than that of somatic stem cells; also in cancer cells . "Octamer" means "consisting of eight parts" and refers to the binding sequence "ATTTGCAT" in the promoter region of target genes.

genetics

In humans, the Oct-4 gene is located on chromosome 6 , gene locus 6p21.33.

function

The Oct-4 gene codes for a protein - a transcription factor - that is important for normal embryonic development . The protein has two isoforms with different molar masses (A: 45 kDa , B: 33 kDa). Oct-4 is selectively expressed in those areas of the embryo where the fetal tissue will later build up. Oct-4 is a vital gene for the development of all mammals . In the adult organism, however, Oct-4 is only expressed in germ cells.

2002 by a working group led by Hans R. Schöler at the University of Pennsylvania in the animal model mouse discovered that the correct expression of Oct-4 is directly correlated with the viability of mouse clones. The activation of Oct-4 must be in a very specific range. Activities that were slightly too low, but also too high, led to the death of the test animals. Depending on the development phase of the embryo, “switching off” Oct-4 has a different effect. In the very early embryonic phase, the loss of Oct-4 causes totipotent cells in the embryo to be converted into trophoblastic cells. In a later phase causes the Oct-4-loss that, in the primordial germ cells to apoptosis is triggered.

As a transcription factor, the gene product of Oct-4 shows highly complex, in some cases not yet known or understood, interactions with other transcription and cofactors from the POU family , but also other families such as Pax or Sox . So Oct-4 can interact with another Oct-4, but also with Oct-1 , Oct-6 or Sox-2 .

Biotechnological research

In the artificial reprogramming of stem cells that is currently being discussed and researched in many laboratories , Oct-4, for example, together with the genes Sox-2 , Nanog and lin-28, is smuggled into somatic cells with the help of retroviruses , whereupon these are converted into pluripotent stem cells.

Since stem cell genes such as Oct-4 are often active in malignant cells, the regulation of this gene is of great scientific interest. Some small RNA molecules, so-called microRNAs , have already been found that up or down regulate the translation of Oct-4.

Individual evidence

  1. ^ Hans R. Schöler, Siegfried Ruppert, Noriaki Suzuki, Kamal Chowdhury & Peter Gruss: New type of POU domain in germ line-specific protein Oct-4. Nature 344: 435-439 (March 29, 1990); doi: 10.1038 / 344435a0
  2. ↑ Norah ME Fogarty, Afshan McCarthy, Kirsten E. Snijders, Benjamin E. Powell, Nada Kubikova, Paul Blakeley, Rebecca Lea, Kay Elder, Sissy E. Wamaitha, Daesik Kim, Valdone Maciulyte, Jens Kleinjung, Jin-Soo Kim, Dagan Wells, Ludovic Vallier, Alessandro Bertero, James MA Turner, Kathy K. Niakan: Genome editing reveals a role for OCT4 in human embryogenesis. In: Nature. 2017, doi : 10.1038 / nature24033 .
  3. ↑ Sc-5279 at scbt.com.
  4. ↑ a b c H. R. Schöler: Trophoblast gene expression and function of genes in the germ line of the mouse. In: Activity report of the Max Planck Society 2004, pp. 87–93.
  5. ↑ J. Yu et al .: Induced pluripotent stem cell lines derived from human somatic cells. In: Science 318, pp. 1917-1920, 2007. PMID 18029452
  6. ↑ K. Okita et al .: Generation of germline-competent induced pluripotent stem cells. In: Nature 448, pp. 313-317, 2007. PMID 17554338
  7. ↑ K. Takahashi and S. Yamanaka: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. In: Cell 126, pp. 663-676, 2006. PMID 16904174
  8. ↑ Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Cell Stem Cell. 2011 Apr 8; 8 (4): 376-88.
  9. ↑ MicroRNA cluster 302-367 enhances somatic cell reprogramming by accelerating a mesenchymal-to-epithelial transition. Liao B, Bao X, Liu L, Feng S, Zovoilis A, Liu W, Xue Y, Cai J, Guo X, Qin B, Zhang R, Wu J, Lai L, Teng M, Niu L, Zhang B, Esteban MA , Pei D. J Biol Chem. 2011 May 13; 286 (19): 17359-64. Epub 2011 Mar 22.
  10. ↑ microRNA-145 suppresses lung adenocarcinoma-initiating cell proliferation by targeting OCT4.Yin R, Zhang S, Wu Y, Fan X, Jiang F, Zhang Z, Feng D, Guo X, Xu L., Oncol Rep. 2011 Jun; 25 (6): 1747-54. doi: 10.3892 / or.2011.1252 . Epub 2011 Apr 7
  11. ↑ Up-regulation of microRNA-145 promotes differentiation by repressing OCT4 in human endometrial adenocarcinoma cells. Wu Y, Liu S, Xin H, Jiang J, Younglai E, Sun S, Wang H. Cancer. 2011 Sep 1; 117 (17): 3989-98. doi: 10.1002 / cncr.25944 . Epub 2011 Mar 1.

literature

  • HR Schöler et al: New type of POU domain in germ line-specific protein Oct-4. In: Nature 344, 1990, pp. 435-439.
  • J. Kehler et al .: Oct-4 is required for primordial germ cell survival. In: EMBO Reports 5, 2004, pp. 1078-1083.
  • J. Maurer et al .: Contrasting expression of keratins in mouse and human embryonic stem cells. In: PLoS ONE 3, 2008, e3451. PMID 18941637
  • V. Chickarmane, C. Peterson: A computational model for understanding stem cell, trophectoderm and endoderm lineage determination. In: PLoS ONE 3, 2008, e3478. PMID 18941526
  • Y. Sun et al .: Evolutionarily conserved transcriptional co-expression guiding embryonic stem cell differentiation. In: PLoS ONE 3, 2008, e3406. PMID 18923680
  • D. Qin et al .: Mouse meningiocytes express Sox2 and yield high efficiency of chimeras after nuclear reprogramming with exogenous factors. In: J Biol Chem 283, pp. 33730-33735, 2008 PMID 18826945
  • D. Pei: Regulation of pluripotency and reprogramming by transcription factors. In: J. Biol. Chem. 284, 2009, pp. 3365-3369, PMID 18819918 (review).
  • T. Wilhelm: Development and application of new analytical methods for the differentiation of murine embryonic stem cells. Dissertation, Eberhard Karls University of Tübingen, 2008, DNB 990032701/34

Non-scientific publications

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