Alternative titles; symbols
HGNC Approved Gene Symbol: ID4
Cytogenetic location: 6p22.3 Genomic coordinates (GRCh38): 6:19,837,370-19,842,197 (from NCBI)
Transcription factors containing a basic helix-loop-helix (bHLH) motif regulate expression of tissue-specific genes in a number of mammalian and insect systems. DNA-binding activity of the bHLH proteins is dependent on formation of homo- and/or heterodimers. Dominant-negative HLH proteins encoded by Id-related genes, such as ID4, also contain the HLH-dimerization domain but lack the DNA-binding basic domain. Consequently, Id proteins inhibit binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins (Pagliuca et al., 1995).
Pagliuca et al. (1995) reported the cDNA sequence of a novel human HLH gene, ID4, which lacks the basic domain. ID4 is differentially expressed in adult organs as 4 mRNA molecules that are presumably the result of differential splicing and/or alternative polyadenylation sites.
Transfection experiments by Pagliuca et al. (1995) indicated that enforced expression of the ID4 protein inhibits the transactivation of the muscle creatine kinase (CKM; 123310) E-box enhancer by MyoD (MYOD1; 159970).
Yu et al. (2005) found aberrant Id4 methylation in a mouse model of T-lymphoblastic leukemia following leukemic transformation, but not in the benign preleukemic phase. ID4 was silenced by promoter methylation in the majority of human leukemias examined, but not in normal bone marrow, normal lymphocytes, or other tumor types. Transfection of mouse Id4 into a mouse lymphoid tumor inhibited cell growth in vitro and in SCID mice in vivo. Yu et al. (2005) concluded that ID4 is a putative tumor suppressor.
By fluorescence in situ hybridization (FISH), Pagliuca et al. (1995) mapped the ID4 gene to 6p22-p21.3. By the same method, Rigolet et al. (1998) mapped the gene to 6p23-p22.3.
Pagliuca, A., Bartoli, P. C., Saccone, S., Valle, G. D., Lania, L. Molecular cloning of ID4, a novel dominant negative helix-loop-helix human gene on chromosome 6p21.3-p22. Genomics 27: 200-203, 1995. [PubMed: 7665172] [Full Text: https://doi.org/10.1006/geno.1995.1026]
Rigolet, M., Rich, T., Gross-Morand, M.-S., Molina-Gomes, D., Viegas-Pequignot, E., Junien, C. cDNA cloning, tissue distribution and chromosomal localization of the human ID4 gene. DNA Res. 5: 309-313, 1998. [PubMed: 9872455] [Full Text: https://doi.org/10.1093/dnares/5.5.309]
Yu, L., Liu, C., Vandeusen, J., Becknell, B., Dai, Z., Wu, Y.-Z., Raval, A., Liu, T.-H., Ding, W., Mao, C., Liu, S., Smith, L. T., Lee, S., Rassenti, L., Marcucci, G., Byrd, J., Caligiuri, M. A., Plass, C. Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nature Genet. 37: 265-274, 2005. [PubMed: 15723065] [Full Text: https://doi.org/10.1038/ng1521]