Noshiro Mitsuhide, Furukawa Masae, Honma Sato, Kawamoto Takeshi, Hamada Taizo, Honma Ken-ichi, Kato Yukio
Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
J Biol Rhythms. 2005 Oct;20(5):404-18. doi: 10.1177/0748730405280195.
DEC1 and DEC2-basic helix-loop-helix transcription factors-exhibit a circadian expression in the suprachiasmatic nucleus and other peripheral tissues and seem to play roles in regulating the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoters of Per1, Dec1, and Dec2. The authors present data on the expression patterns of mRNA for Dec1, Dec2, Per2, Dbp, and Npas2 in various tissues of wild-type and homozygous Clock mutant mice (Clock/Clock). The Clock mutation resulted in extreme reduction of Dec1 expression in kidney, heart, and skeletal muscle but not in liver, whereas it strongly repressed Dec2 expression in liver, kidney, and heart, while Dec2 expression in skeletal muscle remained rhythmic. Per2 also showed the tissue-dependent disruption of the rhythmicity by Clock mutation, whereas rhythmic expression of Dbp in Clock mutant mice disappeared in all tissues examined. Npas2, a structurally and functionally related gene to Clock, showed significant levels of expression in the liver and kidney with a robust rhythmicity, which was also affected by Clock mutation. These marked changes in the Dec1 and Dec2 expression, as well as in the Per2, Dbp, and Npas2 expression in the periphery by Clock mutation, indicated that CLOCK plays a major role in the expression of these genes in most tissues. However, circadian expression of Dec1 in liver and kidney and that of Dec2 in skeletal muscle of Clock mutant mice suggested that CLOCK-independent circadian regulation operates in some tissues.
DEC1和DEC2（碱性螺旋-环-螺旋转录因子）在视交叉上核及其他外周组织中呈现昼夜节律性表达，并且似乎通过抑制Per1、Dec1和Dec2的CLOCK/BMAL1激活启动子，在调节哺乳动物昼夜节律中发挥作用。作者展示了野生型和纯合Clock突变小鼠（Clock/Clock）各组织中Dec1、Dec2、Per2、Dbp和Npas2的mRNA表达模式数据。Clock突变导致肾脏、心脏和骨骼肌中Dec1表达极度减少，但肝脏中未出现这种情况，而它强烈抑制肝脏、肾脏和心脏中的Dec2表达，同时骨骼肌中Dec2表达仍保持节律性。Per2也显示出因Clock突变导致的组织依赖性节律紊乱，而Clock突变小鼠中Dbp的节律性表达在所有检测组织中均消失。Npas2是与Clock在结构和功能上相关的基因，在肝脏和肾脏中表达水平显著且具有较强的节律性，其也受到Clock突变的影响。Clock突变导致外周组织中Dec1和Dec2表达以及Per2、Dbp和Npas2表达出现这些显著变化，表明CLOCK在大多数组织中这些基因的表达中起主要作用。然而，Clock突变小鼠肝脏和肾脏中Dec1的昼夜节律性表达以及骨骼肌中Dec2的昼夜节律性表达表明，在某些组织中存在不依赖CLOCK的昼夜节律调节。
