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鸡端粒酶RNA基因:病毒、禽类和哺乳动物基因组间序列、调控元件及同线性的保守性

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

作者信息

Delany M E, Daniels L M

机构信息

Department of Animal Science, University of California, Davis, CA 95616, USA.

出版信息

Cytogenet Genome Res. 2003;102(1-4):309-17. doi: 10.1159/000075768.

DOI:10.1159/000075768
PMID:14970722
Abstract

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.

摘要

端粒酶RNA(TR)对于端粒酶活性以及增殖细胞群体中端粒长度的维持至关重要。本研究的目的是确定鸡TR(chTR)的细胞遗传学和分子基因组组织。chTR以单拷贝基因(TERC,别名TR)的形式存在,定位于9号染色体(GGA9)。GGA9长臂上的位点在人类中映射到三条染色体,其中九个GGA9q位点中的五个映射到HSA3q。对UCD 001基因组(红原鸡)的chTERC位点(3763 bp)进行测序,包括:5'端604 bp、465 bp的编码区以及3'端2694 bp(从-604到+3159)。序列分析包括在多个层面进行的同源性搜索,包括不同鸡基因型、马立克氏病病毒(MDV)序列以及人类和小鼠之间的比较。我们提供了chTERC与MDV基因组之间5'端和3'端远端序列同源性的证据,以及其他已知同源区域(启动子和编码区)的证据,详细阐述了不同基因组中5'端转录因子结合基序,并展示了鸡TR 3'端TERT相关基序的类型和数量(例如,Sp1、c-Myb、c-Myc、AP2等)。该基因周围有超过25个Sp1位点、20多个癌基因转录因子结合基序以及众多激素和其他特殊结合基序。了解chTERC 5'端和3'端调控元件将有助于研究生长和发育过程中的正常控制机制,以及研究肿瘤发生过程中这个重要基因失调的可能性,特别是在不同基因型之间。

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