Alternative titles; symbols
HGNC Approved Gene Symbol: ELK4
Cytogenetic location: 1q32.1 Genomic coordinates (GRCh38): 1:205,607,943-205,632,011 (from NCBI)
Regulation of gene expression often involves the interaction of transcription factors to form multicomponent complexes at promoter and enhancer elements. For example, transcriptional regulation of the FOS gene (164810) in response to growth factor stimulation appears to involve a multicomponent complex at the serum response element (SRE). This complex contains the ubiquitous nuclear protein SRF together with a second protein, ternary complex factor (TCF), which cannot bind the SRE by itself. Dalton and Treisman (1992) employed a genetic screen using yeast to identify SAP1, an SRF accessory protein, which has DNA binding properties identical to those of TCF. Subsequently, they identified a related protein, SAP2 (600247), by its cDNA sequence homology with the SAP1 cDNA. These proteins contain 3 regions of homology to a third protein, ELK1 (311040), which also functions as an SRF accessory protein and is immunologically related to HeLa cell TCF. The SAP1, SAP2, and ELK1 mRNAs are ubiquitous.
Mo et al. (1998) determined the crystal structures of the conserved ETS domain of SAP1 bound to DNA sequences from the E74 and c-fos promoters. These structures revealed that a set of conserved residues contact a GGA core DNA sequence. Discrimination for sequences outside this core is mediated by DNA contacts from conserved and nonconserved protein residues and sequence-dependent DNA structural properties characteristic of A-form DNA structure. Modeling studies of a SAP1/SRF/DNA complex suggested that SRF may modulate SAP1 binding to DNA by interacting with its ETS domain.
Shipley et al. (1994) used cDNA probes to isolate cosmid and phage clones harboring genes encoding SAP1 and SAP2. With these clones, they mapped the genes to 1q32 and 12q23, respectively, by fluorescence in situ hybridization. Giovane et al. (1995) likewise mapped ELK4 to human 1q32 by in situ hybridization. By the same method, they mapped the mouse homolog to chromosome 1E3-G.
Using gene targeting and T-cell receptor (TCR) transgenic approaches, Costello et al. (2004) characterized the function of Elk4 in mouse thymocyte development. Flow cytometric analysis demonstrated reduced numbers of single-positive thymocytes and peripheral T-cell numbers. TCR-induced activation of Elk4 target genes, such as Egr1 (128990), was impaired in double-positive thymocytes, although Erk (EPHB2; 600997) activation was normal. Analysis of TCR transgenes showed a requirement for Elk4 in positive, but not negative, selection and that the defect in Elk4 heterozygotes was only moderate.
Costello, P. S., Nicolas, R. H., Watanabe, Y., Rosewell, I., Treisman, R. Ternary complex factor SAP-1 is required for Erk-mediated thymocyte positive selection. Nature Immun. 5: 289-298, 2004. [PubMed: 14770179] [Full Text: https://doi.org/10.1038/ni1038]
Dalton, S., Treisman, R. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell 68: 597-612, 1992. Note: Erratum: Cell 76: 411 only, 1994. [PubMed: 1339307] [Full Text: https://doi.org/10.1016/0092-8674(92)90194-h]
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]
Mo, Y., Vaessen, B., Johnston, K., Marmorstein, R. Structures of SAP-1 bound to DNA targets from the E74 and c-fos promoters: insights into DNA sequence discrimination by Ets proteins. Molec. Cell 2: 201-212, 1998. [PubMed: 9734357] [Full Text: https://doi.org/10.1016/s1097-2765(00)80130-6]
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]