Kudo Toshiyuki, Sutou Shizuyo
Laboratory of Functional Genomics, Department of Biological Pharmacy, School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Okayama 703-8516, Japan.
Gene. 2006 Feb 15;367:38-45. doi: 10.1016/j.gene.2005.08.026. Epub 2006 Jan 5.
Liver receptor homolog-1 (LRH-1) is a homolog of FTZ-F1, a transcription factor of the fruit fly, and belongs to the orphan nuclear receptor family. LRH-1 is expressed in organs derived from the endoderm, including intestine, liver and exocrine pancreas and plays a predominant role in development, bile-acid homeostasis, and reverse cholesterol transport. Recent research has revealed that mammalian LRH-1 is also expressed in the steroidogenic organs and has suggested that LRH-1 shares a role in steroidogenesis with steroidogenic factor-1 (SF-1), which is a paralog of LRH-1. In this study, we determined transcription initiation sites of chicken LRH-1 and showed that LRH-1 is expressed as several splicing variants in chicken steroidogenic organs. From three steroidogenic organs, the adrenal glands, ovaries, and testes, several cDNA fragments including different lengths and sequences were amplified by 5'-RACE and these were mainly classified into five types. Using these sequences, chicken genomic database was searched and four types of first exons were identified in chromosome 8. However, the database sequence of these regions included several gaps. So we cloned gap regions by PCR cloning from chicken genomic DNA and found the other type of first exons in the gaps. Moreover, RT-PCR showed the expression of LRH-1 in chicken steroidogenic organs as many splicing variants. We concluded that the chicken LRH-1 gene is transcribed from at least five different transcription initiation sites and alternative splicing produces several types of mRNA in steroidogenic organs.
肝脏受体同源物-1(LRH-1)是果蝇转录因子FTZ-F1的同源物,属于孤儿核受体家族。LRH-1在内胚层来源的器官中表达,包括肠道、肝脏和外分泌胰腺,并在发育、胆汁酸稳态和胆固醇逆向转运中起主要作用。最近的研究表明,哺乳动物LRH-1也在类固醇生成器官中表达,并提示LRH-1与类固醇生成因子-1(SF-1)在类固醇生成中具有共同作用,SF-1是LRH-1的旁系同源物。在本研究中,我们确定了鸡LRH-1的转录起始位点,并表明LRH-1在鸡类固醇生成器官中以多种剪接变体的形式表达。从三个类固醇生成器官,即肾上腺、卵巢和睾丸中,通过5'-RACE扩增出了几个包括不同长度和序列的cDNA片段,这些片段主要分为五种类型。利用这些序列搜索鸡基因组数据库,在8号染色体上鉴定出四种类型的第一外显子。然而,这些区域的数据库序列包含几个缺口。因此,我们通过PCR克隆从鸡基因组DNA中克隆缺口区域,并在缺口中发现了另一种类型的第一外显子。此外,RT-PCR显示LRH-1在鸡类固醇生成器官中以多种剪接变体的形式表达。我们得出结论,鸡LRH-1基因至少从五个不同的转录起始位点转录,并且可变剪接在类固醇生成器官中产生几种类型的mRNA。