HGNC Approved Gene Symbol: LYL1
Cytogenetic location: 19p13.13 Genomic coordinates (GRCh38) : 19:13,099,033-13,102,858 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 19p13.13 | Leukemia, T-cell acute lymphoblastoid | 151440 | 2 |
LYL1 is a member of the large basic helix-loop-helix family of transcription factors and has a role in angiogenesis (Pirot et al., 2010).
Cleary et al. (1988) isolated DNA spanning a t(7;19) chromosomal translocation breakpoint from a human T-cell line established from an acute lymphoblastic leukemia. Nucleotide sequence analysis showed that the point of crossover on chromosome 7 occurred immediately adjacent to a joining segment within the TCRB gene (see 186930), suggesting that this translocation resulted from an error in TCR gene rearrangement. On chromosome 19, the translocation occurred within a previously uncharacterized transcriptional unit for which Cleary et al. (1988) proposed the designation LYL1. An RNA of about 1.5 kb was transcribed from this gene in a wide variety of hematolymphoid cell lines. The t(7;19) resulted in truncation of the LYL1 gene and production of abnormal-sized RNAs, suggesting a role for LYL1 in the pathogenesis of this leukemia.
Using quantitative RT-PCR, Pirot et al. (2010) found that Lyl1 was expressed in all mouse tissues examined, with highest expression in spleen. LYL1 was also expressed in human umbilical vein endothelial cells (HUVECs), with higher expression in HUVECs undergoing quiescence.
Pirot et al. (2010) found that silencing of LYL1 in HUVECs and hTERT1 cells via small interfering RNA and short hairpin RNA, respectively, did not affect endothelial tubulogenesis in 3-dimensional cultures. However, vessels formed from LYL1-depleted cells were less organized compared with controls and showed abnormal VE-cadherin (CDH5; 601120) staining. LYL1 depletion in hTERT1 cells and HUVECs was associated with reduced expression of molecules associated with endothelial cell adhesion and vessel stability, including activated RAP1 (see RAP1A; 179520), the RAP1 activators C3G (RAPGEF1; 600303) and DOCK4 (607679), and alpha-2 integrin (ITGA2; 192974).
Cleary et al. (1988) identified the LYL1 gene on chromosome 19. By fluorescence in situ hybridization, Trask et al. (1993) assigned the LYL1 gene to 19p13.2-p13.1. Kuo et al. (1991) mapped the mouse Lyl-1 gene to chromosome 8, thereby defining a new region of homology of synteny with human 19p. The mapping was achieved in an interspecific backcross using a RFLP. The predicted mouse Lyl1 protein was 78% identical to human LYL1.
Pirot et al. (2010) stated that Lyl1 disruption in mice results in moderate hematopoietic defects, but not in major developmental abnormalities. They found that LLC lung cancer and B16-F10 melanoma tumors grew faster in Lyl1 -/- mice than in controls or Lyl1 +/- littermates. Lyl1 -/- vessels showed accelerated growth in 3-dimensional gels and aortic ring assays compared with controls. Tumor blood vessels from Lyl1 -/- mice exhibited angiogenic features, including poor pericyte coverage, increased vascular leakage, lumen enlargement, and persistent Tal1 (187040) expression. Tumors in Lyl11 -/- mice also exhibited increased expression of the proangiogenic factor Ang2 (ANGPT2; 601922), which plays a central role in vessel maturation and stabilization. Pirot et al. (2010) concluded that LYL1 does not initiate vascular outgrowth, but that it is involved in vessel stabilization.
Cleary, M. L., Mellentin, J. D., Spies, J., Smith, S. D. Chromosomal translocation involving the beta T cell receptor gene in acute leukemia. J. Exp. Med. 167: 682-687, 1988. [PubMed: 3162254] [Full Text: https://doi.org/10.1084/jem.167.2.682]
Kuo, S. S., Mellentin, J. D., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Cleary, M. L. Structure, chromosome mapping, and expression of the mouse Lyl-1 gene. Oncogene 6: 961-968, 1991. [PubMed: 2067848]
Pirot, N., Deleuze, V., El-Hajj, R., Dohet, C., Sablitzky, F., Couttet, P., Mathieu, D., Pinet, V. LYL1 activity is required for the maturation of newly formed blood vessels in adulthood. Blood 115: 5270-5279, 2010. [PubMed: 20418284] [Full Text: https://doi.org/10.1182/blood-2010-03-275651]
Trask, B., Fertitta, A., Christensen, M., Youngblom, J., Bergmann, A., Copeland, A., de Jong, P., Mohrenweiser, H., Olsen, A., Carrano, A., Tynan, K. Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers. Genomics 15: 133-145, 1993. [PubMed: 8432525] [Full Text: https://doi.org/10.1006/geno.1993.1021]