Alternative titles; symbols
HGNC Approved Gene Symbol: DBP
Cytogenetic location: 19q13.33 Genomic coordinates (GRCh38): 19:48,630,030-48,637,379 (from NCBI)
DBP is a member of the PAR bZIP (proline and acidic amino acid-rich basic leucine zipper) transcription factor family (Khatib et al., 1994).
Using the bZIP domain of TEF (188595) to probe an acute B-leukemia cell line cDNA library, Khatib et al. (1994) cloned DBP. The deduced 325-amino acid protein contains PAR, DNA-binding, and leucine zipper domains in its C-terminal half. Northern blot analysis detected a 1.8-kb transcript in all cell lines and tissues tested except liver, which appeared to contain degraded DBP mRNA.
Gachon et al. (2004) stated that the expression of 3 PAR bZIP transcription factors, TEF, DBP, and HLF (142385), show high-amplitude circadian expression in the suprachiasmatic nucleus, the master circadian pacemaker in mammals. However, they are expressed at nearly invariable levels in most brain regions, in which clock gene expression only cycles with low amplitude. RT-PCR of mouse tissues demonstrated that all 3 transcription factors show higher amplitude circadian cycles of expression in liver than in brain. Genes regulated by the PAR bZIP transcription factors showed similar circadian cycles of expression, with higher amplitude in mouse liver. Transcriptome profiling revealed that pyridoxal kinase (PDXK; 179020), a coenzyme of many enzymes involved in amino acid and neurotransmitter metabolism, is a target gene for PAR bZIP proteins in liver and brain.
Toward a system-level understanding of the transcriptional circuitry regulating circadian clocks, Ueda et al. (2005) identified clock-controlled elements on 16 clock and clock-controlled genes in a comprehensive surveillance of evolutionarily conserved cis elements and measurement of the transcriptional dynamics. Ueda et al. (2005) found that E boxes (CACGTG) and E-prime boxes (CACGTT) controlled the expression of Per1 (602260), Nr1d2 (602304), Per2 (603426), Nr1d1 (602408), Dbp, Bhlhb2 (604256), and Bhlhb3 (606200) transcription following a repressor-precedes-activator pattern, resulting in delayed transcriptional activity. RevErbA/ROR (600825)-binding elements regulated the transcriptional activity of Arntl (602550), Npas2 (603347), Nfil3 (605327), Clock (601851), Cry1 (601933), and Rorc (602943) through a repressor-precedes-activator pattern as well. DBP/E4BP4-binding elements controlled the expression of Per1, Per2, Per3 (603427), Nr1d1, Nr1d2, Rora, and Rorb (601972) through a repressor-antiphasic-to-activator mechanism, which generates high-amplitude transcriptional activity. Ueda et al. (2005) suggested that regulation of E/E-prime boxes is a topologic vulnerability in mammalian circadian clocks, a concept that had been functionally verified using in vitro phenotype assay systems.
Shutler et al. (1996) determined that the DBP gene contains 4 exons and spans about 6 kb.
Szpirer et al. (1992) mapped the gene encoding DBP to human chromosome 19 and rat chromosome 1 by means of somatic cell hybrids segregating either human or rat chromosomes. The transcription factor encoded by DBP is related to that encoded by CEBP (116897). The 2 genes are syntenic in man and rat.
Using fluorescence in situ hybridization, Khatib et al. (1994) mapped the DBP gene to 19q13. The assignment was confirmed by a study of human chromosome segregation in somatic cell hybrids. Stubbs et al. (1996) mapped DBP to 19q13.3 by hybridization to cosmid clones that had previously been mapped to that region by high-resolution FISH mapping methods. They mapped the mouse homolog to chromosome 7 by interspecific backcross analysis.
Gachon et al. (2004) found that mice homozygous for Hlf and Tef mutant alleles were morphologically normal and fertile. Animals devoid of any 2 or 3 PAR bZIP transcription factors were anatomically normal and fertile, but those lacking all 3 had dramatically shortened life span. Within the first month after birth, homozygous triple-knockout mice developed spontaneous epilepsy characterized by myoclonic, tonic-clonic, and possibly absence seizures, in addition to audiogenic seizure susceptibility. PAR bZIP-deficient mice show decreased brain levels of pyridoxal-5-phosphate, serotonin, and dopamine. Gachon et al. (2004) concluded that the expression of some clock-controlled genes may have to remain within narrow limits in the brain and undergo only low-amplitude cycles of expression in most brain regions.
Gachon, F., Fonjallaz, P., Damiola, F., Gos, P., Kodama, T., Zakany, J., Duboule, D., Petit, B., Tafti, M., Schibler, U. The loss of circadian PAR bZip transcription factors results in epilepsy. Genes Dev. 18: 1397-1412, 2004. [PubMed: 15175240] [Full Text: https://doi.org/10.1101/gad.301404]
Khatib, Z. A., Inaba, T., Valentine, M., Look, A. T. Chromosomal localization and cDNA cloning of the human DBP and TEF genes. Genomics 23: 344-351, 1994. [PubMed: 7835883] [Full Text: https://doi.org/10.1006/geno.1994.1510]
Shutler, G., Glassco, T., Kang, X., Korneluk, R., Mueller, C. R. Genomic structure of the human D-site binding protein (DBP) gene. Genomics 34: 334-339, 1996. [PubMed: 8786133] [Full Text: https://doi.org/10.1006/geno.1996.0295]
Stubbs, L., Carver, E., Ashworth, L., Lopez-Molina, L. Location of the DBP transcription factor gene in human and mouse. Mammalian Genome 7: 65-67, 1996. [PubMed: 8903733] [Full Text: https://doi.org/10.1007/s003359900016]
Szpirer, C., Riviere, M., Cortese, R., Nakamura, T., Islam, M. Q., Levan, G., Szpirer, J. Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF). Genomics 13: 293-300, 1992. [PubMed: 1535333] [Full Text: https://doi.org/10.1016/0888-7543(92)90245-n]
Ueda, H. R., Hayashi, S., Chen, W., Sano, M., Machida, M., Shigeyoshi, Y., Iino, M., Hashimoto, S. System-level identification of transcriptional circuits underlying mammalian circadian clocks. Nature Genet. 37: 187-192, 2005. [PubMed: 15665827] [Full Text: https://doi.org/10.1038/ng1504]