The chicken telomerase RNA gene: conservation of sequence, regulatory elements and synteny among viral, avian and mammalian genomes

摘要

Telomerase RNA (TR) is essential for telomerase activity and the maintenance of telomere length in proliferating cell populations. The objective of the present research was to define the cytogenetic and molecular genomic organization of chicken TR (chTR). The chTR exists as a single copy gene (TERC, alias TR), mapping to chromosome 9 (GGA9). The loci on the q arm of GGA9 map to three chromosomes in human with five of the nine GGA9q loci mapping to HSA3q. Sequencing of the chTERC locus (3,763 bp) from the UCD 001 genome (Red Jungle Fowl) included: 604 bp 5', 465 coding, and 2,694 bp 3' (from -604 to +3159). Sequence analysis included homology searches conducted on several levels including comparisons among different chicken genotypes, Marek's disease virus (MDV) sequences, plus human and murine. We provide evidence for distal 5' and 3' sequence homology between chTERC and the MDV genome among other known regions of homology (promoter and coding), elaborate on 5' transcription factor binding motifs among the various genomes as well as show type and number of TERT-related motifs 3' of chicken TR (e.g., Sp1, c-Myb, c-Myc, AP2, among others). Surrounding the gene are more than 25 Sp1 sites, over 20 oncogene transcription factor binding motifs and numerous hormonal and other specialized binding motifs. Knowledge of 5' and 3' chTERC regulatory elements will be useful for investigating normal control mechanisms during growth and development as well as investigating the potential for dysregulation of this important gene during oncogenesis, especially among different genotypes.