Selected targets of Oct-3/4

Selected targets of Oct-3/4

A transcription factor POU class 5 homeobox 1 ( Oct-3/4 ) isan essential mediator of the embryonic stem cell state, It has been implicated in lineagespecific differentiation, adult stem cell identity, and cancer [1], [2], [3], [4]. Effects produced by Oct-3/4 in thecell depend on its functional partners (e.g., SRY (sex determining region Y)-box 2 (SOX2 ), High-mobility group box 1 ( HMG1 ) and others) [1],[5].

Oct-3/4 activates transcription of a wide number of proteinsthat participate in developmental signaling and early differentiation, such as:

. Ligands, e.g., Fibroblast growth factor 4 (FGF4 ) [6], Tumor necrosis factor (ligand) superfamily member 11 (RANKL(TNFSF11) ) [7], Inhibin beta B ( Activin beta B ) [8], [7].

. receptors, e.g., Platelet-derived growthfactor receptor alpha polypeptide (PDGF -R-alpha ) [9], Fibroblastgrowth factor receptor 2 ( FGFR2 ) [8].

. transcription factors, e.g., SOX2[10], Nanog homeobox ( NANOG ) [11], Eomesodermin[12]

Oct-3/4 regulates transcription of Chorionic gonadotropin betapolypeptide ( CGB ) that is essential for the maintenance of pregnancy [13].

In addition, mechanisms to actively repress apoptotic pathways areinvolved in maintaining the stem cell state [4]. One of the most importantof these genes are Caspase-6 [4] and Cell death-inducing DFFA-likeeffector a ( CIDE-A ) [7].

1. Pesce M, Sch??ler HR
   Oct-4: gatekeeper in the beginnings of mammalian development. Stem cells (Dayton, Ohio) 2001;19(4):271-8
2. Takeda J, Seino S, Bell GI
   Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic acids research 1992 Sep 11;20(17):4613-20
3. Stefanovic S, Puc??at M
   Oct-3/4: not just a gatekeeper of pluripotency for embryonic stem cell, a cell fate instructor through a gene dosage effect. Cell cycle (Georgetown, Tex.) 2007 Jan 1;6(1):8-10
4. Campbell PA, Perez-Iratxeta C, Andrade-Navarro MA, Rudnicki MA
   Oct4 targets regulatory nodes to modulate stem cell function. PLoS ONE 2007 Jun 20;2(6):e553
5. Okumura-Nakanishi S, Saito M, Niwa H, Ishikawa F
   Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. The Journal of biological chemistry 2005 Feb 18;280(7):5307-17
6. Ambrosetti DC, Basilico C, Dailey L
   Synergistic activation of the fibroblast growth factor 4 enhancer by Sox2 and Oct-3 depends on protein-protein interactions facilitated by a specific spatial arrangement of factor binding sites. Molecular and cellular biology 1997 Nov;17(11):6321-9
7. Sharov AA, Masui S, Sharova LV, Piao Y, Aiba K, Matoba R, Xin L, Niwa H, Ko MS
   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 2008 Jun 3;9(1):269
8. Matoba R, Niwa H, Masui S, Ohtsuka S, Carter MG, Sharov AA, Ko MS
   Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling. PLoS ONE 2006 Dec 20;1:e26
9. Kraft HJ, Mosselman S, Smits HA, Hohenstein P, Piek E, Chen Q, Artzt K, van Zoelen EJ
   Oct-4 regulates alternative platelet-derived growth factor alpha receptor gene promoter in human embryonal carcinoma cells. The Journal of biological chemistry 1996 May 31;271(22):12873-8
10. Chew JL, Loh YH, Zhang W, Chen X, Tam WL, Yeap LS, Li P, Ang YS, Lim B, Robson P, Ng HH
    Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Molecular and cellular biology 2005 Jul;25(14):6031-46
11. Rodda DJ, Chew JL, Lim LH, Loh YH, Wang B, Ng HH, Robson P
    Transcriptional regulation of nanog by OCT4 and SOX2. The Journal of biological chemistry 2005 Jul 1;280(26):24731-7
12. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA
    Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 2005 Sep 23;122(6):947-56
13. Liu L, Roberts RM
    Silencing of the gene for the beta subunit of human chorionic gonadotropin by the embryonic transcription factor Oct-3/4. The Journal of biological chemistry 1996 Jul 12;271(28):16683-9