Genes & Development：基因改造可延长苍蝇生物钟周期

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生物谷报道：日本理化研究所的一个研究小组近日成功在苍蝇体内发现生物钟的遗传基因，改变这些基因会导致苍蝇的生物钟周期延长两小时。

据日本《朝日新闻》日前报道，研究小组对于影响苍蝇生活规律的137个基因分别进行改造，然后观察这些改造对苍蝇生活规律的影响。研究发现，如果把苍蝇体内一种名为“CWO”的基因关闭，使其不再发挥作用，那么苍蝇的生物钟周期从原先的24小时变成了26小时。

研究小组负责人上田泰己说，“今后还将进一步研究‘CWO’基因和其他生物钟基因的关系，这一研究可为揭开人类生物钟的秘密提供帮助。”

日本研究人员的这一发现刊登在最新一期美国《基因与发育》杂志网站上。（引自新华网）




原始出处：

Published online before print June 19, 2007
Genes and Development, DOI: 10.1101/gad.1552607

Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component
Sebastian Kadener1, Dan Stoleru1,2, Michael McDonald3, Pipat Nawathean1,2, and Michael Rosbash1,2,4
1 Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA; 2 Howard Hughes Medical Institute and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454, USA; 3 Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA


Many organisms use circadian clocks to keep temporal order and anticipate daily environmental changes. In Drosophila, the master clock gene Clock promotes the transcription of several key target genes. Two of these gene products, PER and TIM, repress CLK–CYC-mediated transcription. To recognize additional direct CLK target genes, we designed a genome-wide approach and identified clockwork orange (cwo) as a new core clock component. cwo encodes a transcriptional repressor that synergizes with PER and inhibits CLK-mediated activation. Consistent with this function, the mRNA profiles of CLK direct target genes in cwo mutant flies manifest high trough values and low amplitude oscillations. Because behavioral rhythmicity fails to persist in constant darkness (DD) with little or no effect on average mRNA levels in flies lacking cwo, transcriptional oscillation amplitude appears to be linked to rhythmicity. Moreover, the mutant flies are long period, consistent with the late repression indicated by the RNA profiles. These findings suggest that CWO acts preferentially in the late night to help terminate CLK–CYC-mediated transcription of direct target genes including cwo itself. The presence of mammalian homologs with circadian expression features (Dec1 and Dec2) suggests that a similar feedback mechanism exists in mammalian clocks.


[Keywords: Circadian; clk; Drosophila; transcriptional oscillations; chromatin]

Received March 16, 2007; revised version accepted May 14, 2007.