DIFFERENT PATTERNS OF GENE-EXPRESSION OF TOPOISOMERASE-II ISOFORMS IN DIFFERENTIATED TISSUES DURING MURINE DEVELOPMENT
DIFFERENT PATTERNS OF GENE-EXPRESSION OF TOPOISOMERASE-II ISOFORMS IN DIFFERENTIATED TISSUES DURING MURINE DEVELOPMENT
复制标题
DOI：
10.1016/0167-4781(92)90050-a
复制
发表时间：
1992-08-17
期刊：
影响因子：
--
通讯作者：
ZUNINO, F
中科院分区：
文献类型：
--
作者：
CAPRANICO, G;TINELLI, S;ZUNINO, F
本文研究了DNA拓扑异构酶II-α和β-基因在小鼠正常组织中的表达。使用针对这两个基因的探针进行Northern杂交分析表明，这两个基因在成年小鼠22个组织中的表达模式不同。拓扑异构酶II-α基因在增生性组织(如骨髓和脾)中高表达，在其他17种组织中检测不到或低表达。相比之下，在成年小鼠的各种组织(15)中发现了拓扑异构酶II-β基因的高或中等表达，包括那些没有增殖细胞的组织。还研究了拓扑异构酶II基因在小鼠发育过程中的表达。在整个胚胎中，这两个基因在胚胎发育早期的表达水平高于胚胎发育的晚期。出生前两天胚胎的心脏、大脑和肝脏以及这些组织加上新生(1日龄)小鼠的肺和胸腺表达了这两个基因的显著水平。有趣的是，β基因的表达在出生后在大脑中被观察到，但在肝脏中没有；相反，α基因在出生后1天在肝脏中的表达增加，但在大脑中没有。然而，在胚胎和新生儿的这些组织中，增殖相关酶胸苷合成酶的基因表达是相似的。因此，这两个基因在出生后时期受到不同的调控，这两个同工酶在脑和肝脏等分化组织的发育中可能具有组织特异性的作用。根据这两种异构体的差异表达模式，这一分析表明拓扑异构酶II-α可能是细胞增殖的特异性标志，而拓扑异构酶II-β可能参与DNA代谢而不是复制功能。
The expression of DNA topoisomerase II-alpha and beta-genes was studied in murine normal tissues. Northern blot analysis using probes specific for the two genes showed that the patterns of expression were different among 22 tissues of adult mice. Expression levels of topoisomerase II-alpha-gene were high in proliferating tissues, such as bone marrow and spleen, and undetectable or low in 17 other tissues. In contrast, high or intermediate expression of topoisomerase II-beta-gene was found in a variety of tissues (15) of adult mice, including those with no proliferating cells. Topoisomerase II gene expression was also studied during murine development. In whole embryos both genes were expressed at higher levels in early than late stages of embryogenesis. Heart, brain and liver of embryos two days before delivery, and these same tissues plus lung and thymus of newborn (1-day-old) mice expressed appreciable levels of the two genes. Interestingly, a post-natal induction of the beta-gene expression was observed in the brain but not in the liver; conversely, the expression of the alpha-gene was increased 1 day after birth in the liver but not in the brain. However, gene expression of a proliferation-associated enzyme, thymidylate synthase, was similar in these tissues between embryos and newborns. Thus, the two genes were differentially regulated in the post-natal period, and a tissue-specific role may be suggested for the two isoenzymes in the development of differentiated tissues such as the brain and liver. Based on the differential patterns of expression of the two isoforms, this analysis indicates that topoisomerase II-alpha may be a specific marker of cell proliferation, whereas topoisomerase II-beta may be implicated in functions of DNA metabolism other than replication.