Li X, Chen S, Wang Q, Zack D J, Snyder S H, Borjigin J
Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1876-81. doi: 10.1073/pnas.95.4.1876.
The circadian hormone melatonin is synthesized predominantly in the pineal gland by the actions of two pineal-specific enzymes: serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). Pineal night-specific ATPase (PINA), another pineal- and night-specific protein we recently identified, is produced as a truncated form of the Wilson disease gene (Atp7b) product. To identify the regulatory elements required for pineal-specific gene expression, we isolated sequences upstream of the rat PINA gene and discovered a cis-acting element that is recognized by a novel pineal/retina-specific nuclear factor. This pineal regulatory element (PIRE) has a consensus of TAATC/T and is present in six copies in the 5' regulatory region of the PINA gene, at least three copies in the rat NAT promoter, and at least one copy in each of the putative HIOMT promoters A and B. A recently identified retina-specific protein, cone rod homeobox (CRX), binds to PIRE in vitro and transactivates PIRE-reporter constructs. These data suggest that Crx may play a crucial role in regulating pineal gene expression through interactions with PIRE.
血清素N - 乙酰基转移酶（NAT）和羟基吲哚 - O - 甲基转移酶（HIOMT）。松果体夜间特异性ATP酶（PINA）是我们最近鉴定出的另一种松果体和夜间特异性蛋白，它是威尔逊病基因（Atp7b）产物的截短形式。为了鉴定松果体特异性基因表达所需的调控元件，我们分离了大鼠PINA基因上游的序列，并发现了一种由新型松果体/视网膜特异性核因子识别的顺式作用元件。这种松果体调控元件（PIRE）的共有序列为TAATC/T，在PINA基因的5'调控区域中有六个拷贝，在大鼠NAT启动子中有至少三个拷贝，在假定的HIOMT启动子A和B中各有至少一个拷贝。最近鉴定出的一种视网膜特异性蛋白，视锥视杆同源框（CRX），在体外与PIRE结合并激活PIRE - 报告基因构建体。这些数据表明，Crx可能通过与PIRE相互作用在调节松果体基因表达中发挥关键作用。
