Alternative titles; symbols
HGNC Approved Gene Symbol: ETV5
Cytogenetic location: 3q27.2 Genomic coordinates (GRCh38): 3:186,046,314-186,109,089 (from NCBI)
For background information on ETS (164720)-related transcription factors, see ETV3 (164873).
Monte et al. (1994) isolated a human testis cDNA for ERM (ETV5), an Ets-related transcription factor. The 2.2-kb ERM clone encoded a 510-amino acid putative protein which shares about 95% identity with the mouse genes Pea3 and Er81 in the 85-residue DNA-binding ETS domain. ERM is about 85% identical with these proteins within the N-terminal acidic domain. Further, the protein was shown to bind to an oligonucleotide containing the consensus nucleotide core sequence GGAA recognized by the other Ets proteins.
Monte et al. (1994) showed that ERM is widely expressed in human cell lines and tissues (except for normal lymphocytes) and is especially high in brain and placenta. In mouse tissues, Pea3 and Er81 mRNAs displayed restricted patterns of expression, whereas ERM was widely expressed in human tissues.
Monte et al. (1996) determined that the human ERM gene contains 14 exons distributed over 65 kb of genomic DNA.
Monte et al. (1996) mapped the ETV5 gene to chromosome 3q27-q29 by in situ hybridization. Protopopova et al. (1996) mapped the gene to 3q28 by fluorescence in situ hybridization.
Chen et al. (2005) showed that ERM is expressed exclusively within Sertoli cells in the testis and is required for spermatogonial stem cell self-renewal. Mice with targeted disruption of ERM have a loss of maintenance of spermatogonial stem cell self-renewal without a block in normal spermatogenic differentiation and thus have progressive germ cell depletion and a Sertoli cell-only syndrome. Microarray analysis of primary Sertoli cells from Erm-deficient mice showed alterations in secreted factors known to regulate the hematopoietic stem cell niche. Chen et al. (2005) concluded that their results identify a new function for the Ets family transcription factors in spermatogenesis and provide an example of transcriptional control of a vertebrate stem cell niche.
Using a yeast 2-hybrid assay with a human brain cDNA library, Pastorcic and Das (2007) found that ERM bound full-length ZNF237 (ZMYM5; 616443). Both full-length ZNF237 and a truncated isoform repressed expression of a PS1 (PSEN1; 104311) reporter when expressed in a human neuroblastoma cell line. Deletion analysis suggested that the N-terminal region of ZNF237 was required for interaction with ERM and for translational repression. EMSA revealed formation of a high molecular mass DNA-protein complex between the PS1 promoter region and in vitro-translated ZNF237 and ERM.
Vitari et al. (2011) identified COP1 (608067) as a tumor suppressor that negatively regulates ETV1 (600541), ETV4 (600711), and ETV5. ETV1, which is mutated in prostate cancer more often, was degraded after being ubiquitinated by COP1. Truncated ETV1 encoded by prostate cancer translocation TMPRSS2:ETV1 lacks the critical COP1 binding motifs and was 50-fold more stable than wildtype ETV1. Almost all patient translocations render ETV1 insensitive to COP1, implying that this confers a selective advantage to prostate epithelial cells. Indeed, COP1 deficiency in mouse prostate elevated ETV1 and produced increased cell proliferation, hyperplasia, and early prostate intraepithelial neoplasia. Combined loss of COP1 and PTEN (601728) enhanced the invasiveness of mouse prostate adenocarcinomas. Finally, rare human prostate cancer samples showed hemizygous loss of the COP1 gene, loss of COP1 protein, and elevated ETV1 protein while lacking a translocation event. Vitari et al. (2011) concluded that their findings identified COP1 as a tumor suppressor whose downregulation promotes prostatic epithelial cell proliferation and tumorigenesis.
Lu et al. (2009) found that Etv4 (600711) and Etv5 are expressed at the ureteric bud tip, and that they are among a set of genes upregulated by Gdnf (600837)-Ret (164761) signaling during mouse kidney development. Knockout of Etv5 was embryonic lethal prior to kidney development; however, both Etv4 -/- embryos and Etv4 +/- Etv5 +/- compound heterozygotes appeared grossly normal but occasionally showed renal agenesis, and Etv4 -/- Etv5 +/- newborn mice showed hypoplastic or missing kidneys. Lu et al. (2009) identified several genes whose expression in the ureteric bud depended on Etv4 and Etv5, including Cxcr4 (162643), Myb (189990), Met (164860), and Mmp14 (600754). The authors concluded that ETV4 and ETV5 play a role in branching morphogenesis in the developing kidney.
Chen, C., Ouyang, W., Grigura, V., Zhou, Q., Carnes, K., Lim, H., Zhao, G.-Q., Arber, S., Kurpios, N., Murphy, T. L., Cheng, A. M., Hassell, J. A., Chandrashekar, V., Hofmann, M.-C., Hess, R. A., Murphy, K. M. ERM is required for transcriptional control of the spermatogonial stem cell niche. (Letter) Nature 436: 1030-1034, 2005. [PubMed: 16107850] [Full Text: https://doi.org/10.1038/nature03894]
Lu, B. C., Cebrian, C., Chi, X., Kuure, S., Kuo, R., Bates, C. M., Arber, S., Hassell, J., MacNeil, L., Hoshi, M., Jain, S., Asai, N., Takahashi, M., Schmidt-Ott, K. M., Barasch, J., D'Agati, V., Costantini, F. Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nature Genet. 41: 1295-1302, 2009. Note: Erratum: Nature Genet. 42: 361 only, 2010. [PubMed: 19898483] [Full Text: https://doi.org/10.1038/ng.476]
Monte, D., Baert, J. L., Defossez, P. A., de Launoit, Y., Stehelin, D. Molecular cloning and characterization of human ERM, a new member of the Ets family closely related to mouse PEA3 and ER81 transcription factors. Oncogene 9: 1397-1406, 1994. [PubMed: 8152800]
Monte, D., Coutte, L., Dewitte, F., Defossez, P.-A., Le Coniat, M., Stehelin, D., Berger, R., de Launoit, Y. Genomic organization of the human ERM (ETV5) gene, a PEA3 group member of ETS transcription factors. Genomics 35: 236-240, 1996. [PubMed: 8661127] [Full Text: https://doi.org/10.1006/geno.1996.0345]
Pastorcic, M., Das, H. K. Analysis of transcriptional modulation of the presenilin 1 gene promoter by ZNF237, a candidate binding partner of the Ets transcription factor ERM. Brain Res. 1128: 21-32, 2007. [PubMed: 17126306] [Full Text: https://doi.org/10.1016/j.brainres.2006.10.056]
Protopopova, M. V., Vorobieva, N. V., Protopopov, A. I., Gizatullin, R. Z., Kashuba, V. I., Klein, G., Zabarovsky, E. R., Graphodatsky, A. S. Assignment of the ERM gene (ETV5) coding for the ets-related protein to human chromosome band 3q28 by in situ hybridization. Cytogenet. Cell Genet. 74: 220 only, 1996. [PubMed: 8941378] [Full Text: https://doi.org/10.1159/000134419]
Vitari, A. C., Leong, K. G., Newton, K., Yee, C., O'Rourke, K., Liu, J., Phu, L., Vij, R., Ferrando, R., Couto, S. S., Mohan, S., Pandita, A., Hongo, J.-A., Arnott, D., Wertz, I. E., Gao, W.-Q., French, D. M., Dixit, V. M. COP1 is a tumour suppressor that causes degradation of ETS transcription factors. Nature 474: 403-406, 2011. [PubMed: 21572435] [Full Text: https://doi.org/10.1038/nature10005]