Alternative titles; symbols
HGNC Approved Gene Symbol: SPRY3
Cytogenetic location: Xq28 Genomic coordinates (GRCh38): X:155,612,586-155,782,459 (from NCBI)
Hacohen et al. (1998) found that the Drosophila sprouty gene encodes a novel cysteine-rich protein that defines a new family of putative signaling molecules that may similarly function as fibroblast growth factor antagonists in vertebrate development. See SPRY1 (602465). By amino acid homology searches of databases, Hacohen et al. (1998) identified and cloned 3 different human homologs, SPRY1, SPRY2 (602466), and SPRY3, of the Drosophila sprouty gene. A partial sequence of the human SPRY3 gene was identified.
De Bonis et al. (2006) determined that the SPRY3 gene contains 2 exons and has a long 3-prime untranslated region. The translation initiation codon resides in exon 2. Luciferase reporter assay showed strongest promoter activity within a 1-kb region spanning the transcription start site. Sequence analysis did not find canonic CpG islands within a 20-kb region centered on the promoter.
In their determination of the DNA sequence of the human X chromosome, Ross et al. (2005) demonstrated that the SPRY3 gene is located on the X chromosome in the second pseudoautosomal region (PAR2) at the telomeric end of the long arm. A homolog is located on the Y chromosome (see their Table 1).
De Bonis et al. (2006) reported that silencing of the SPRY3 gene appeared to be independent of DNA methylation. PCR analysis showed no signs of differential methylation between expressed and silent alleles. In contrast to SYBL1 (VAMP7; 300053), another repressed PAR2 gene, inactive X and Y alleles of SPRY3 were not reactivated in cells treated with a DNA methylation inhibitor or in cells from ICF syndrome (242860) patients, who have mutations in the DNA methyltransferase-3B gene (DNMT3B; 602900). SPRY3 X- and Y-inactivation was associated with a differential enrichment of repressive histone modifications and the recruitment of Polycomb group proteins (see, e.g., EZH2; 601573) compared to the active X allele. Another major factor in SPRY2 repression was late replication: the active X and Y alleles of SPRY3 had delayed replication relative to the active X allele, even in ICF syndrome cells in which the closely linked SYBL1 gene was reactivated and advanced in replication. The relatively stable maintenance of SPRY3 silencing compared to SYBL1 led De Bonis et al. (2006) to suggest that genes without CpG islands might be less prone to reactivation than previously thought, and that genes with CpG islands may require promoter methylation as an additional layer of repression.
De Bonis, M. L., Cerase, A., Matarazzo, M. R., Ferraro, M., Strazzullo, M., Hansen, R. S., Chiurazzi, P., Neri, G., D'Esposito, M. Maintenance of X- and Y-inactivation of the pseudoautosomal (PAR2) gene SPRY3 is independent from DNA methylation and associated to multiple layers of epigenetic modifications. Hum. Molec. Genet. 15: 1123-1132, 2006. [PubMed: 16500999] [Full Text: https://doi.org/10.1093/hmg/ddl027]
Hacohen, N., Kramer, S., Sutherland, D., Hiromi, Y., Krasnow, M. A. Sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell 92: 253-263, 1998. [PubMed: 9458049] [Full Text: https://doi.org/10.1016/s0092-8674(00)80919-8]
Ross, M. T., Grafham, D. V., Coffey, A. J., Scherer, S., McLay, K., Muzny, D., Platzer, M., Howell, G. R., Burrows, C., Bird, C. P., Frankish, A., Lovell, F. L., and 270 others. The DNA sequence of the human X chromosome. Nature 434: 325-337, 2005. [PubMed: 15772651] [Full Text: https://doi.org/10.1038/nature03440]