Widespread expression of the bovine Agouti gene results from at least three alternative promoters

Widespread expression of the bovine Agouti gene results from at least three alternative promoters
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DOI:
10.1111/j.1600-0749.2004.00195.x
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发表时间:
2005-02-01
期刊:
PIGMENT CELL RESEARCH
影响因子:
--
通讯作者:
Oulmouden, A
Oulmouden, A
中科院分区:
其他
文献类型:
--
作者:
Girardot, M;Martin, J;Oulmouden, A

文献摘要

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在野生型小鼠中,众所周知,Agouti 仅在皮肤中表达,它控制带状毛发表型。作为研究刺豚鼠在牛中生理作用的第一步,我们分离了相应的基因并研究了其表达模式。我们没有发现代表大量毛色表型的八个品种内部和之间编码区序列变异的证据。我们通过 Northern 杂交在大脑、心脏、肺、肝脏、肾脏、脾脏中检测到两种 Agouti mRNA 亚型,在皮肤中检测到第三种亚型。我们对皮肤中的全长 Agouti 转录本进行了表征,并分离了在其他组织中表达的两个 mRNA 的 5'UTR。三种 mRNA 具有相同的编码区,但 5' 非翻译区不同。上游调控序列显示两个替代启动子,涉及除皮肤以外的组织中的广泛表达。有趣的是,这些序列与直系同源的人类(76-85% 同一性)和猪(82-86% 同一性)ASIP 基因的上游序列高度同源。除了其在色素沉着中的潜在作用(如在小鼠中所见)之外,我们认为牛刺豚鼠可能还参与多种生理功能。此外,牛、猪和人类调控序列之间的显着同源性表明这些直系同源基因受到类似的调控。最后,由于许多真核 mRNA 的 5'UTR 具有生理相关性,因此讨论了它们对牛 Agouti mRNA 性能的影响。
In wild-type mice, it is well known that Agouti is only expressed in skin where it controls the banded-hair phenotype. As a first step to investigate the physiological role of Agouti in cattle, we isolated the corresponding gene and studied its expression pattern. We found no evidence of coding-region sequence variation within and between eight breeds representing a large panel of coat colour phenotypes. We detected by northern hybridization two Agouti mRNA isoforms in brain, heart, lung, liver, kidney, spleen and a third in skin. We characterized the full-length Agouti transcript in skin and isolated the 5'UTR of two mRNAs expressed in the other tissues. The three mRNAs have the same coding region but differ by their 5' untranslated regions. Upstream regulatory sequences display two alternative promoters involved with the broad expression in tissues other than skin. Interestingly, these sequences are highly homologous to upstream sequences of the orthologous human (76-85% identity) and pig (82-86% identity) ASIP genes. In addition to its potential role in pigmentation (as seen in mice), we suggest that bovine Agouti could be involved in various physiological functions. Furthermore, the significant homology between cattle, pig and human regulatory sequences indicate that these orthologous genes are regulated alike. Lastly, since the 5'UTR of many eukaryotic mRNAs are physiologically relevant, their impact on bovine Agouti mRNA performance is discussed.