CHRONO and DEC1/DEC2 compensate for lack of CRY1/CRY2 in expression of coherent circadian rhythm but not in generation of circadian oscillation in the neonatal mouse SCN.
CHRONO and DEC1/DEC2 compensate for lack of CRY1/CRY2 in expression of coherent circadian rhythm but not in generation of circadian oscillation in the neonatal mouse SCN.
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DOI：
10.1038/s41598-021-98532-5
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发表时间：
2021-09-28
影响因子：
4.6
通讯作者：
Honma S
中科院分区：
文献类型：
--
作者：
Ono D;Honma KI;Schmal C;Takumi T;Kawamoto T;Fujimoto K;Kato Y;Honma S
时钟基因Cry1和Cry2是核心分子反馈环的抑制成分，被认为是哺乳动物昼夜节律产生的关键分子。Cry1和Cry2的双重敲除可以消除成年小鼠在持续黑暗条件下的昼夜行为节律。然而，在培养的Cry1/Cry2缺陷新生小鼠的视交叉上核(SCN)中检测到PER2：：Luc强劲的昼夜节律表达，并通过与野生型新生SCN的共同培养在成年SCN中恢复表达。这些发现使我们推测在昼夜节律的产生中，Cry1/Cry2缺乏的补偿分子(S)。我们研究了Chrono和Dec1/Dec2蛋白的作用，它们是PER(S)转录的抑制因子，类似于Cay(S)。意外的是，在Cry1/Cry2缺陷小鼠中，Chrono或Dec1/Dec2的敲除并没有取消一致的昼夜节律，而是将其分离成三个不同的周期，或者显著缩短了新生SCN的昼夜节律周期。对Cry1/Cry2基因缺陷小鼠SCN的基因芯片分析显示，PER(S)、Chrono和Dec(S)的表达显著增加，表明BMAL1/CLOCK抑制了该反式激活。在这里，我们得出结论，Chrono和Dec1/Dec2不能弥补昼夜节律生成中CRY1/CRY2的缺失，但有助于新生小鼠SCN中连贯的昼夜节律表达，很可能是通过整合细胞昼夜节律。
Clock genes Cry1 and Cry2, inhibitory components of core molecular feedback loop, are regarded as critical molecules for the circadian rhythm generation in mammals. A double knockout of Cry1 and Cry2 abolishes the circadian behavioral rhythm in adult mice under constant darkness. However, robust circadian rhythms in PER2::LUC expression are detected in the cultured suprachiasmatic nucleus (SCN) of Cry1/Cry2 deficient neonatal mice and restored in adult SCN by co-culture with wild-type neonatal SCN. These findings led us to postulate the compensatory molecule(s) for Cry1/Cry2 deficiency in circadian rhythm generation. We examined the roles of Chrono and Dec1/Dec2 proteins, the suppressors of Per(s) transcription similar to CRY(s). Unexpectedly, knockout of Chrono or Dec1/Dec2 in the Cry1/Cry2 deficient mice did not abolish but decoupled the coherent circadian rhythm into three different periodicities or significantly shortened the circadian period in neonatal SCN. DNA microarray analysis for the SCN of Cry1/Cry2 deficient mice revealed substantial increases in Per(s), Chrono and Dec(s) expression, indicating disinhibition of the transactivation by BMAL1/CLOCK. Here, we conclude that Chrono and Dec1/Dec2 do not compensate for absence of CRY1/CRY2 in the circadian rhythm generation but contribute to the coherent circadian rhythm expression in the neonatal mouse SCN most likely through integration of cellular circadian rhythms.
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DOI：
10.15252/embj.2020106745
发表时间：
2021-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Putker M;Wong DCS;Seinkmane E;Rzechorzek NM;Zeng A;Hoyle NP;Chesham JE;Edwards MD;Feeney KA;Fischer R;Peschel N;Chen KF;Vanden Oever M;Edgar RS;Selby CP;Sancar A;O'Neill JS
通讯作者：
O'Neill JS
影响因子：
3.7
作者：
Rossner, Moritz J.;Oster, Henrik;Wichert, Sven P.;Reinecke, Lisa;Wehr, Michael C.;Reinecke, Johannes;Eichele, Gregor;Taneja, Reshma;Nave, Klaus-Armin
通讯作者：
Nave, Klaus-Armin
影响因子：
3.7
作者：
Ono D;Honma S;Honma K
通讯作者：
Honma K
影响因子：
64.8
作者：
Ueda, HR;Chen, WB;Hashimoto, S
通讯作者：
Hashimoto, S
影响因子：
5.3
作者：
Nakashima, Ayumu;Kawamoto, Takeshi;Kato, Yukio
通讯作者：
Kato, Yukio