Alternative titles; symbols
HGNC Approved Gene Symbol: TSC22D4
Cytogenetic location: 7q22.1 Genomic coordinates (GRCh38): 7:100,466,519-100,479,214 (from NCBI)
TSC22D4 is a member of the TSC22 domain family of leucine zipper transcriptional regulators (see TSC22D3; 300506) (Kester et al., 1999; Fiorenza et al., 2001).
By yeast 2-hybrid screening of a mouse brain cDNA library using TSC22D1 (607715) as bait, followed by database analysis, Kester et al. (1999) cloned human and mouse TSC22D4, which they called THG1. The deduced 395-amino acid human protein contains a TSC box and leucine zipper region and has a calculated molecular mass of 41 kD. TSC22D4 shares similarity with TSC22D1, TSC22D3, KIAA0669, and Drosophila 'shortsighted' shs over the TSC box leucine zipper domain.
Fiorenza et al. (2001) used differential screening by subtractive hybridization of cDNAs isolated from embryonic day 12.5 wildtype and Lhx3 (LHX4; 602146) mutant mouse pituitaries to clone mouse Tsc22d4, which they called Thg-1pit. The 387-amino acid mouse protein shares 79% amino acid identity with human TSC22D4.
Fiorenza et al. (2001) showed that mouse Tsc22d4 expression in the pituitary cell line GH3 was induced in response to TGF-beta (TGFB1; 190180). RT-PCR assays detected Tsc22d4 expression during mouse embryonic development with expression first detected at stage 98.5 followed by a sharp increase during the next 24 hours that coincided with initiation of Lhx3 expression and preceded formation of the pituitary rudiment. A second increase in Tsc22d4 expression at embryonic day 12.5 coincided with development of Rathke's pouch. Tsc22d4 expression was also detected in the entire central nervous system. In contrast, Tsc22d4 expression in Lhx3 mutant mouse embryos showed an absence of pituitary expression of Tsc22d4 although expression in the rest of the brain was no different from wildtype. Fiorenza et al. (2001) concluded that Tsc22d4 is regulated by Lhx3 during pituitary organogenesis.
By database analysis to identify sequences similar to tilapia osmotic stress transcription factor-1 (OSTF1), Fiol et al. (2007) cloned mouse Tsc22d4. The deduced 387-amino acid proteins has an approximately 70-amino acid C-terminal TSC22D domain and leucine zipper region. Quantitative RT-PCR detected Tsc22d4 expression in mouse kidney cortex, medulla, and papilla, and in mouse IMCD3 inner medullary collecting duct cells.
By yeast 2-hybrid analysis, gel shift assay, and GST pull-down experiments, Kester et al. (1999) confirmed that TSC22D4 interacts with TSC22D1 by forming heterodimers. They demonstrated that TSC22D4 has transcriptional repressor activity.
Fiol et al. (2007) mapped the mouse Tsc22d4 gene to chromosome 5G1.
Hartz (2017) mapped the TSC22D4 gene to chromosome 7q22.1 based on an alignment of the TSC22D4 sequence (GenBank AJ133115) with the genomic sequence (GRCh38).
Fiol, D. F., Mak, S. K., Kultz, D. Specific TSC22 domain transcripts are hypertonically induced and alternatively spliced to protect mouse kidney cells during osmotic stress. FEBS J. 274: 109-124, 2007. [PubMed: 17147695] [Full Text: https://doi.org/10.1111/j.1742-4658.2006.05569.x]
Fiorenza, M. T., Mukhopadhyay, M., Westphal, H. Expression screening for Lhx3 downstream genes identifies Thg-1pit as a novel mouse gene involved in pituitary development. Gene 278: 125-130, 2001. [PubMed: 11707329] [Full Text: https://doi.org/10.1016/s0378-1119(01)00715-6]
Hartz, P. A. Personal Communication. Baltimore, Md. 10/17/2017.
Kester, H. A., Blanchetot, C., den Hertog, J., van der Saag, P. T., van der Burg, B. Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. J. Biol. Chem. 274: 27439-27447, 1999. [PubMed: 10488076] [Full Text: https://doi.org/10.1074/jbc.274.39.27439]