Morris M E, Viswanathan N, Kuhlman S, Davis F C, Weitz C J
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Science. 1998 Mar 6;279(5356):1544-7. doi: 10.1126/science.279.5356.1544.
The mechanism by which mammalian circadian clocks are entrained to light-dark cycles is unknown. The clock that drives behavioral rhythms is located in the suprachiasmatic nucleus (SCN) of the brain, and entrainment is thought to require induction of genes in the SCN by light. A complementary DNA subtraction method based on genomic representational difference analysis was developed to identify such genes without making assumptions about their nature. Four clones corresponded to genes induced specifically in the SCN by light, all of which showed gating of induction by the circadian clock. Among these genes are c-fos and nur77, two of the five early-response genes known to be induced in the SCN by light, and egr-3, a zinc finger transcription factor not previously identified in the SCN. In contrast to known examples, egr-3 induction by light is restricted to the ventral SCN, a structure implicated in entrainment.
哺乳动物生物钟与昼夜明暗周期同步的机制尚不清楚。驱动行为节律的生物钟位于大脑的视交叉上核(SCN),人们认为同步需要光诱导SCN中的基因。我们开发了一种基于基因组代表性差异分析的互补DNA消减方法,用于识别此类基因,而无需对其性质进行假设。四个克隆对应于由光在SCN中特异性诱导的基因,所有这些基因均显示出受生物钟的诱导门控。这些基因包括c-fos和nur77,这是已知的五个在SCN中由光诱导的早期反应基因中的两个,以及egr-3,一种先前未在SCN中鉴定出的锌指转录因子。与已知实例相反,光对egr-3的诱导仅限于腹侧SCN,这是一个与同步有关的结构。