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Clock-dependent and independent transcriptional control of the two isoforms from the mouse Rorgammagene

机译:时钟依赖和独立的转录控制从小鼠Rorgammagene的两个亚型。

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Accumulating evidence indicate that molecular mechanisms generating circadian rhythms display some degree of tissue-specificity. More specifically, distinct patterns of expression for nuclear receptors of the ROR family indicate that the transcriptional control of the clock gene Bmal1 differs among tissues. This study aims to investigate the expression of Rorgammaisoforms (Rorgamma and Rorgammat) and characterize the molecular mechanisms underlying their tissue-specific expression. The expression of Rorgamma isoforms was assessed in mouse liver, muscle, thymus and testis throughout 24 h using quantitative RT-PCR. Although the expression of Rorgamma was rhythmic in the liver and thymus, it was constitutively expressed in muscle and testis. In contrast, the expression of Rorgammat was constitutive in all four tissues. Furthermore, rhythmic expression of Rorgamma was impaired in Clock mutant mice whereas the mutation had no effect on Rorgammat expression. In line with these findings, luciferase assays revealed that transcription of the Rorgamma promoter is clock-controlled whereas that of Rorgammat promoter is essentially clock-independent. Our results provide insights into the molecular mechanisms that lead to differential expression of Rorgamma and Rorgammat and are suggestive of a framework that might account for tissue-specific circadian regulation.
机译:越来越多的证据表明,产生昼夜节律的分子机制显示出一定程度的组织特异性。更具体地说,ROR家族核受体的不同表达模式表明,时钟基因Bmal1的转录控制在组织之间不同。这项研究旨在调查Rorgammaisoforms(Rorgamma和Rorgammat)的表达,并表征其组织特异性表达的分子机制。使用定量RT-PCR评估整个24小时内小鼠肝脏,肌肉,胸腺和睾丸中Rorgamma同工型的表达。尽管Rorgamma在肝脏和胸腺中有节律性表达,但在肌肉和睾丸中组成性表达。相反,在所有四个组织中,Rorgammat的表达都是组成型的。此外,在Clock突变小鼠中Rorgamma的节律性表达受损,而该突变对Rorgammat的表达没有影响。与这些发现一致,荧光素酶测定法揭示了Rorgamma启动子的转录是时钟控制的,而Rorgammat启动子的转录基本上是时钟独立的。我们的结果提供了导致Rorgamma和Rorgammat差异表达的分子机制的见解,并暗示了一个可能解释组织特异性生物钟调节的框架。

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