Alternative titles; symbols
HGNC Approved Gene Symbol: ELK3
Cytogenetic location: 12q23.1 Genomic coordinates (GRCh38): 12:96,194,375-96,269,824 (from NCBI)
The ETS gene family encodes a group of proteins that function as transcription factors under physiologic conditions and, if aberrantly expressed, can cause cellular transformation. Lopez et al. (1994) cloned the gene for a new ETS-related transcription factor, which they called ERP for 'ETS-related protein,' from a murine pre-B cell line and from lung tissue. The ERP protein contained a region of high homology with the ETS DNA-binding domain common to all members of the ETS transcription factor/oncoprotein family. Within the B-cell lineage, ERP is highly expressed primarily at early stages of B-lymphocyte development, and expression declines drastically upon B-cell maturation, correlating with the activity of the enhancer of immunoglobulin heavy chain. The data suggested that ERP plays a role in both B-cell development and IgH gene regulation.
Giovane et al. (1994) identified the same ETS family member, which they designated Net, from Ras-transformed mouse fibroblasts using PCR primers based on the nucleotide sequence corresponding to the most conserved amino acids of the ETS domain. They subsequently obtained a complete cDNA sequence. The predicted Net protein contains an ETS domain at the amino terminus that is about 80% similar to the human ELK1 (311040) and ELK4 (600246) sequences. The authors noted that 2 other domains also show significant similarity to regions of these proteins, and that the 3 genes clearly belong to the ELK family. Two mRNAs of 2.5 and 4.5 kb were detected by Northern blotting. Transcripts were found, at varying levels, in a large number of transformed cell lines and tissues.
Giovane et al. (1994) showed that Net protein bound to ETS DNA motifs and could form complexes with SRF (600589) on the fos serum response element.
Using fluorescence in situ hybridization, Shipley et al. (1994) mapped ELK4 and ELK3 to 1q32 and 12q23, respectively. (The authors referred to ELK4 as SAP1 and to ELK3 as SAP2.) Tamai et al. (1995) mapped the Elk3 gene to mouse chromosome 10 and suggested that the human homolog (ELK3) may be located on 12q in the interval between bands q21 and q24 because of established homology of synteny with the mid-distal region of mouse chromosome 10. Giovane et al. (1995) mapped ELK3 to human 12q22-q23 and to mouse 10C-D1 by in situ hybridization.
By gene targeting, Ayadi et al. (2001) developed mice expressing a mutant Elk3 that lacked the Ets DNA-binding domain. Homozygous mutant mice developed a vascular defect and upregulated Egr1 (128990) expression in heart and pulmonary arteries by embryonic day 18.5 (E18.5). Mutant mice died after birth due to respiratory failure resulting from the accumulation of chyle in the thoracic cage. Mutants had dilated lymphatic vessels as early as E16.5. Using promoter reporter assays with Elk3 antisense sequences and mutation analysis, Ayadi et al. (2001) determined that Elk3 negatively regulates Egr1 expression and specifically binds SRE5 of the Egr1 promoter. They hypothesized that Erg1 dysfunction could be responsible for obstructions that ultimately affect the lymphatics.
Ayadi, A., Zheng, H., Sobieszczuk, P., Buchwalter, G., Moerman, P., Alitalo, K., Wasylyk, B. Net-targeted mutant mice develop a vascular phenotype and up-regulate egr-1. EMBO J. 20: 5139-5152, 2001. [PubMed: 11566878] [Full Text: https://doi.org/10.1093/emboj/20.18.5139]
Giovane, A., Pintzas, A., Maira, S.-M., Sobieszczuk, P., Wasylyk, B. Net, a new ets transcription factor that is activated by Ras. Genes Dev. 8: 1502-1513, 1994. [PubMed: 7958835] [Full Text: https://doi.org/10.1101/gad.8.13.1502]
Giovane, A., Sobieszczuk, P., Mignon, C., Mattei, M.-G., Wasylyk, B. Locations of the ets subfamily members net, elk1, and sap1 (ELK3, ELK1, and ELK4) on three homologous regions of the mouse and human genomes. Genomics 29: 769-772, 1995. [PubMed: 8575773] [Full Text: https://doi.org/10.1006/geno.1995.9938]
Lopez, M., Oettgen, P., Akbarali, Y., Dendorfer, U., Libermann, T. A. ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development. Molec. Cell. Biol. 14: 3292-3309, 1994. [PubMed: 7909357] [Full Text: https://doi.org/10.1128/mcb.14.5.3292-3309.1994]
Shipley, J., Sheer, D., Dalton, S., Treisman, R., Patel, K. Mapping of the human SAP1 (SRF accessory protein 1) gene and SAP2, a gene encoding a related protein, to chromosomal bands 1q32 and 12q23, respectively. Genomics 23: 710-711, 1994. [PubMed: 7851904] [Full Text: https://doi.org/10.1006/geno.1994.1564]
Tamai, Y., Taketo, M., Nozaki, M., Seldin, M. F. Mouse Elk oncogene maps to chromosome X and a novel Elk oncogene (Elk3) maps to chromosome 10. Genomics 26: 414-416, 1995. [PubMed: 7601474] [Full Text: https://doi.org/10.1016/0888-7543(95)80232-b]