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小鼠腺嘌呤核苷酸转位酶1和2基因的表达及序列分析

Expression and sequence analysis of the mouse adenine nucleotide translocase 1 and 2 genes.

作者信息

Levy S E, Chen Y S, Graham B H, Wallace D C

机构信息

Emory University School of Medicine, Center for Molecular Medicine, Atlanta, GA 30322, USA.

出版信息

Gene. 2000 Aug 22;254(1-2):57-66. doi: 10.1016/s0378-1119(00)00252-3.

Abstract

Only two isoforms of the adenine nucleotide translocase (Ant) protein have been identified in mouse, as opposed to the three in humans. To determine whether the homologous mouse and human proteins share similar patterns of expression, Northern and Western analyses were performed on several mouse tissues. Mouse Ant1 is expressed at high levels in skeletal muscle and heart, similar to human ANT1. Mouse Ant2 is strongly expressed in all tissues but muscle, in marked contrast to human ANT2. To investigate the molecular basis of these differences, we cloned and sequenced the genomic loci of mouse Ant1 and Ant2, and compared them to the three human ANT loci. The mouse and human ANT1 and ANT2 genes showed substantial homology starting about 300 base pairs (bp) 5' to the coding region and continuing through the 3' untranslated region (UTR). Repeats constituted 32% of 15kb of Ant1 sequence and 36% of the 27kb of Ant2 sequence and included SINEs, LINEs and LTR elements. The core promoters of the mouse and human ANT1 and ANT2 genes are very similar. However, the mouse Ant1 gene lacks the upstream OXBOX and REBOX elements found in human ANT1 genes, thought to be important for muscle-specific expression. The mouse Ant2 gene, like human ANT2, has an upstream GRBOX, yet this element is not associated with suppression of transcription, as hypothesized for human ANT2. These discrepancies indicate that additional studies will be required to fully understand the transcriptional regulation of both Ant1 and Ant2.

摘要

与人类有三种腺嘌呤核苷酸转位酶(Ant)蛋白亚型不同,在小鼠中仅鉴定出两种。为了确定同源的小鼠和人类蛋白是否具有相似的表达模式,对几种小鼠组织进行了Northern和Western分析。小鼠Ant1在骨骼肌和心脏中高水平表达,与人类ANT1相似。小鼠Ant2在除肌肉外的所有组织中均强烈表达,这与人类ANT2形成显著对比。为了研究这些差异的分子基础,我们克隆并测序了小鼠Ant1和Ant2的基因组位点,并将它们与人类的三个ANT位点进行比较。小鼠和人类的ANT1及ANT2基因在编码区上游约300个碱基对(bp)处开始,一直到3'非翻译区(UTR)都显示出高度同源性。重复序列占Ant1序列15kb的32%,占Ant2序列27kb的36%,包括短散在核元件(SINEs)、长散在核元件(LINEs)和长末端重复元件(LTR)。小鼠和人类ANT1及ANT2基因的核心启动子非常相似。然而,小鼠Ant1基因缺乏人类ANT1基因中发现的上游OXBOX和REBOX元件,这些元件被认为对肌肉特异性表达很重要。与人类ANT2一样,小鼠Ant2基因有一个上游GRBOX,但该元件并不像对人类ANT2所假设的那样与转录抑制相关。这些差异表明,需要进一步研究以全面了解Ant1和Ant2的转录调控。

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