Alternative titles; symbols
HGNC Approved Gene Symbol: VIS1
Cytogenetic location: 2q14-q21 Genomic coordinates (GRCh38): 2:112,200,001-136,100,000
Using genomic probes derived from cellular sequences flanking 2 integrated proviruses, Askew et al. (1991) cloned viral integration sites from a murine myeloid leukemia cell line. Probes from each of 2 integration sites, His1 and His2, identified rearrangements in a number of leukemia cell lines.
Using Northern blot analysis, Askew et al. (1994) identified His1 transcripts in 4 transformed mouse myeloid cell lines, but not in any normal cell lines examined. Two of these cell lines were derived from retrovirus-induced myeloid leukemias harboring integrated proviruses that drove His1 expression by promoter insertion. The other 2 cell lines expressed a discrete 3-kb His1 RNA, and Askew et al. (1994) cloned the corresponding cDNA. His1 contains multiple small ORFs, but it lacks an extensive ORF, and no protein product was produced during in vitro translation. However, Askew et al. (1994) showed that the His1 RNA is spliced and polyadenylated. His1 is conserved in multiple vertebrate species, including human.
Li et al. (1997) isolated an 8.5-kb human genomic clone homologous to the mouse His1 gene from a lymphocyte genomic library. The mouse and human HIS1 sequences are highly colinear, with several regions of high sequence conservation interspersed with regions of divergence. The mouse and human HIS1 genes share 65% identity over 6.6 kb, with greatest divergence at the 3-prime ends. The 5-prime region flanking the transcriptional start site in mouse His1 is highly conserved in the human gene. Sequence analysis revealed conservation of other putative functional domains in exon 3, intron 1, and intron 2. Southern blot analysis with probes from these regions detected homologs in several other vertebrate species. Like the mouse gene, human HIS1 contains multiple small ORFs, but none of the ORFs in mouse His1 are conserved in human HIS1. Li et al. (1997) concluded that human and mouse HIS1 are unlikely to encode proteins.
Askew et al. (1991) determined that the mouse His1 gene contains 3 exons and spans 6 kb.
Li et al. (1997) reported that the human HIS1 gene has a genomic organization similar to the mouse gene. Human HIS1, but not mouse His1, contains Alu repeats in intron 2 and exon 3. Both genes are A/T rich and contain multiple copies of the mRNA destabilization motif, ATTTA, in exon 3. A variant of the TATA box, TTTAAA, is located upstream of the transcriptional start site in mouse His1, and a related sequence is conserved in human HIS1.
By interspecific backcross analysis, Askew et al. (1991) mapped the His1 locus to mouse chromosome 2 and the His2 locus to mouse chromosome 19. In situ hybridization with a probe from the human homologous region mapped the HIS1 locus to human chromosome 2q14-q21. In mouse, the His1 locus mapped to an area distinct from any known oncogene or common site of integration, but near the proximal breakpoint for a deletion observed in over 90% of radiation-induced leukemias.
HIS1 and HIS2 are symbols previously used for histatin-1 (142701) and histatin-2 (142702), respectively. Thus, the HGM nomenclature committee used VIS1, for 'viral integration site-1,' instead of HIS1, as used by Askew et al. (1991).
Askew, D. S., Bartholomew, C., Buchberg, A. M., Valentine, M. B., Jenkins, N. A., Copeland, N. G., Ihle, J. N. His-1 and His-2: identification and chromosomal mapping of two commonly rearranged sites of viral integration in a myeloid leukemia. Oncogene 6: 2041-2047, 1991. [PubMed: 1682866]
Askew, D. S., Li, J., Ihle, J. N. Retroviral insertions in the murine His-1 locus activate the expression of a novel RNA that lacks an extensive open reading frame. Molec. Cell. Biol. 14: 1743-1751, 1994. [PubMed: 8114708] [Full Text: https://doi.org/10.1128/mcb.14.3.1743-1751.1994]
Li, J., Rhodes, J. C., Askew, D. S. Evolutionary conservation of putative functional domains in the human homolog of the murine His-1 gene. Gene 184: 169-176, 1997. [PubMed: 9031624] [Full Text: https://doi.org/10.1016/s0378-1119(96)00591-4]