HGNC Approved Gene Symbol: ZXDA
Cytogenetic location: Xp11.21 Genomic coordinates (GRCh38) : X:57,905,430-57,910,458 (from NCBI)
Zinc finger proteins are a family of transcription factors that bind DNA via zinc finger structures, which were first described in the Xenopus laevis transcription factor TFIIIA (see 600860). Zinc fingers consist of tandemly repeated units of 28 to 30 amino acids that fold independently into DNA-binding domains. These motifs are characterized by histidine and cysteine residues that are specifically arranged such that they pair tetrahedrally with a single zinc ion. ZXDA and ZXDB (300236) are a pair of duplicated zinc finger genes on chromosome Xp11.21 (Greig et al., 1993).
During a mapping study of Xp11.21, Greig et al. (1993) identified the ZXDA and ZXDB genes. By screening a human fetal brain cDNA library with an ZXDA genomic clone, Greig et al. (1993) isolated partial ZXDA and ZXDB cDNAs. A comparison between 1.2 kb of ZXDA coding sequence and the corresponding sequence of ZXDB revealed 98.7% nucleotide sequence identity. Southern blot analysis detected sequences homologous to the ZXDA and ZXDB genes in a number of placental mammalian species. These data suggested that the ZXDA and ZXDB genes arose from a very ancient and highly conserved gene duplication. The predicted partial ZXDA and ZXDB proteins contain 10 tandem zinc finger motifs. Northern blot analysis showed approximately 6.5-kb ZXDA and ZXDB transcripts. RT-PCR detected ZXDA and ZXDB expression in all human tissues examined, namely heart, lung, muscle, fibroblasts, and lymphoblasts, with ZXDB expressed more highly than ZXDA in every tissue. Both the ZXDA and ZXDB genes are subject to X inactivation.
The ZXDA gene comprises a single exon (Greig et al., 1993)
Using a panel of somatic cell hybrids, Greig et al. (1993) confirmed the mapping of the ZXDA and ZXDB genes to Xp11.21. The ZXDA and ZXDB genes are located within approximately 400 kb of each other.
Using gene silencing and reporter assays, Al-Kandari et al. (2007) showed that ZXDA, like ZXDC (615746), interacted with CIITA (MHC2TA; 600005) and was important in transcriptional activation of major histocompatibility complex (MHC) class II genes. Truncation analysis determined that ZXDA contains a transcription activation domain C-terminal to its zinc finger domain. Coimmunoprecipitation analysis revealed that ZXDC interacted with itself and with ZXDC, and the interactions required their zinc finger domains. Al-Kandari et al. (2007) concluded that association of ZXDA and ZXDC is required for efficient interaction with CIITA in a tripartite complex.
Al-Kandari, W., Koneni, R., Navalgund, V., Aleksandrova, A., Jambunathan, S., Fontes, J. D. The zinc finger proteins ZXDA and ZXDC form a complex that binds CIITA and regulates MHC II gene transcription. J. Molec. Biol. 369: 1175-1187, 2007. [PubMed: 17493635] [Full Text: https://doi.org/10.1016/j.jmb.2007.04.033]
Greig, G. M., Sharp, C. B., Carrel, L., Willard, H. F. Duplicated zinc finger protein genes on the proximal short arm of the human X chromosome: isolation, characterization and X-inactivation studies. Hum. Molec. Genet. 2: 1611-1618, 1993. [PubMed: 8268913] [Full Text: https://doi.org/10.1093/hmg/2.10.1611]