维甲酸通过两个不同的启动子调控人类甲硫氨酸亚砜还原酶A（MSRA）基因。
Retinoic acid regulates the human methionine sulfoxide reductase A (MSRA) gene via two distinct promoters.
作者信息
Pascual Iranzu, Larrayoz Ignacio M, Rodriguez Ignacio R
机构信息
Laboratory of Retinal Cell and Molecular Biology, Mechanisms of Retinal Diseases Section, National Eye Institute, NIH, Bethesda, MD, USA.
出版信息
Genomics. 2009 Jan;93(1):62-71. doi: 10.1016/j.ygeno.2008.09.002. Epub 2008 Oct 25.
Abstract
MSRAs (methionine sulfoxide reductases A) are enzymes that reverse the effects of oxidative damage by reducing methionine sulfoxide back to methionine and recovering protein function. In this study we demonstrate that the transcriptional regulation of the human MSRA gene is complex and driven by two distinct promoters. Both promoters demonstrate high expression in human brain and kidney tissues. The upstream (promoter 1) regulates the msrA1 transcript that codes for the mitochondrial form of MSRA and is highly active in a broad range of cell lines. The downstream promoter (promoter 2) regulates the msrA2/3 transcripts that code for the cytosolic/nuclear forms of MSRA and is generally less active. Promoter 2 contains a 65 bp putative enhancer region that is very active in the retinal pigment epithelium-derived D407 cell line. Both promoters are partially regulated by all-trans retinoic acid via RARA and other RARs.
摘要
甲硫氨酸亚砜还原酶A（MSRAs）是一类酶，可通过将甲硫氨酸亚砜还原为甲硫氨酸并恢复蛋白质功能来逆转氧化损伤的影响。在本研究中，我们证明人类MSRA基因的转录调控是复杂的，由两个不同的启动子驱动。两个启动子在人类脑和肾组织中均表现出高表达。上游启动子（启动子1）调控编码线粒体形式MSRA的msrA1转录本，并且在广泛的细胞系中具有高活性。下游启动子（启动子2）调控编码胞质/核形式MSRA的msrA2/3转录本，其活性通常较低。启动子2包含一个65 bp的假定增强子区域，该区域在视网膜色素上皮衍生的D407细胞系中非常活跃。两个启动子均通过视黄酸受体A（RARA）和其他视黄酸受体（RARs）受到全反式维甲酸的部分调控。
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