• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

生物钟基因的细胞自主昼夜节律需要E-box样元件的直接重复序列。

A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes.

作者信息

Nakahata Yasukazu, Yoshida Mayumi, Takano Atsuko, Soma Haruhiko, Yamamoto Takuro, Yasuda Akio, Nakatsu Toru, Takumi Toru

机构信息

Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.

出版信息

BMC Mol Biol. 2008 Jan 4;9:1. doi: 10.1186/1471-2199-9-1.

DOI:10.1186/1471-2199-9-1
PMID:18177499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2254435/
Abstract

BACKGROUND

The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG). The non-canonical E-boxes or E-box-like sequences have also been reported to be necessary for circadian oscillation.

RESULTS

We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-box or a non-canonical E-box and an E-box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-box or E-box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-box-like elements in their promoter region.

CONCLUSION

We propose a novel possible mechanism regulated by double E-box-like elements, not to a single E-box, for circadian transcriptional oscillation. The direct repeat of the E-box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes.

摘要

背景

哺乳动物生物钟基因的昼夜节律表达基于转录反馈环。已知两种含基本螺旋-环-螺旋（bHLH）PAS（Period-Arnt-Sim）结构域的转录激活因子CLOCK和BMAL1，通过与一种称为E盒（CACGTG）的启动子元件相互作用来调节基因表达。据报道，非典型E盒或E盒样序列对于昼夜节律振荡也是必需的。

结果

我们报道了一种生物钟基因细胞自主昼夜节律转录所需的新顺式元件。这种新元件由一个典型E盒或一个非典型E盒以及一个E盒样序列串联组成，两者之间间隔6个碱基对的短间隔。我们证明，E盒或E盒样序列对于产生细胞自主振荡都是必需的。我们还证实，这两个E元件之间具有恒定长度的间隔核苷酸对于稳定振荡至关重要。此外，通过计算机分析我们得出结论，几个生物钟基因和生物钟调控基因在其启动子区域具有E盒样元件的直接重复序列。

结论

我们提出了一种由双E盒样元件而非单个E盒调控的新型昼夜节律转录振荡机制。本研究中鉴定出的E盒样元件的直接重复序列是产生生物钟基因和生物钟调控基因细胞自主转录振荡所需的最小元件。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/e9c548334afd/1471-2199-9-1-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/2f74d2d98e20/1471-2199-9-1-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/8f81bf11d4c4/1471-2199-9-1-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/61f4e0532750/1471-2199-9-1-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/16671aa90d87/1471-2199-9-1-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/e9c548334afd/1471-2199-9-1-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/2f74d2d98e20/1471-2199-9-1-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/8f81bf11d4c4/1471-2199-9-1-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/61f4e0532750/1471-2199-9-1-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/16671aa90d87/1471-2199-9-1-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec35/2254435/e9c548334afd/1471-2199-9-1-5.jpg

相似文献

1
A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes.生物钟基因的细胞自主昼夜节律需要E-box样元件的直接重复序列。
BMC Mol Biol. 2008 Jan 4;9:1. doi: 10.1186/1471-2199-9-1.
2
Transcriptional oscillation of canonical clock genes in mouse peripheral tissues.小鼠外周组织中经典时钟基因的转录振荡。
BMC Mol Biol. 2004 Oct 9;5:18. doi: 10.1186/1471-2199-5-18.
3
Expression of the gene for Dec2, a basic helix-loop-helix transcription factor, is regulated by a molecular clock system.Dec2基因（一种碱性螺旋-环-螺旋转录因子）的表达受分子时钟系统调控。
Biochem J. 2004 Aug 15;382(Pt 1):43-50. doi: 10.1042/BJ20031760.
4
A BMAL1 mutant with arginine 91 substituted with alanine acts as a dominant negative inhibitor.精氨酸91被丙氨酸取代的BMAL1突变体作为显性负性抑制剂发挥作用。
Gene. 2004 Sep 1;338(2):235-41. doi: 10.1016/j.gene.2004.05.022.
5
Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity.CREB 依赖性信号传导和 CLOCK/BMAL1 活性对 mPeriod 启动子的双峰调节。
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7728-33. doi: 10.1073/pnas.102075599.
6
The molecular mechanism regulating the autonomous circadian expression of Topoisomerase I in NIH3T3 cells.调节NIH3T3细胞中拓扑异构酶I自主昼夜节律表达的分子机制。
Biochem Biophys Res Commun. 2009 Feb 27;380(1):22-7. doi: 10.1016/j.bbrc.2008.12.186. Epub 2009 Jan 10.
7
Modulation of BMAL/CLOCK/E-Box complex activity by a CT-rich cis-acting element.富含CT的顺式作用元件对BMAL/CLOCK/E-Box复合物活性的调控
Mol Cell Endocrinol. 2006 Jun 27;252(1-2):74-81. doi: 10.1016/j.mce.2006.03.007. Epub 2006 May 2.
8
Dual role of the CLOCK/BMAL1 circadian complex in transcriptional regulation.CLOCK/BMAL1昼夜节律复合体在转录调控中的双重作用。
FASEB J. 2006 Mar;20(3):530-2. doi: 10.1096/fj.05-5321fje. Epub 2006 Jan 25.
9
The orphan nuclear receptor RORalpha regulates circadian transcription of the mammalian core-clock Bmal1.孤儿核受体RORα调节哺乳动物核心生物钟基因Bmal1的昼夜节律转录。
Nat Struct Mol Biol. 2005 May;12(5):441-8. doi: 10.1038/nsmb925. Epub 2005 Apr 10.
10
Regulation of the ovine MT1 melatonin receptor promoter: interaction between multiple pituitary transcription factors at different phases of development.绵羊MT1褪黑素受体启动子的调控：发育不同阶段多种垂体转录因子之间的相互作用。
Mol Cell Endocrinol. 2007 Mar 30;268(1-2):59-66. doi: 10.1016/j.mce.2007.01.015. Epub 2007 Feb 1.

引用本文的文献

1
Heat-inactivated Streptococcus pneumoniae augments circadian clock gene expression in zebrafish cells.热灭活肺炎链球菌增强斑马鱼细胞中生物钟基因的表达。
Sci Rep. 2024 Nov 13;14(1):27805. doi: 10.1038/s41598-024-78888-0.
2
Circadian clock dysregulation: a potential mechanism of depression in obstructive sleep apnea patients.昼夜节律失调：阻塞性睡眠呼吸暂停患者抑郁的潜在机制。
Transl Psychiatry. 2024 Oct 7;14(1):423. doi: 10.1038/s41398-024-03134-0.
3
Functional and regulatory diversification of Period genes responsible for circadian rhythm in vertebrates.

本文引用的文献

1
A novel E4BP4 element drives circadian expression of mPeriod2.一种新型E4BP4元件驱动mPeriod2的昼夜节律表达。
Nucleic Acids Res. 2007;35(2):648-55. doi: 10.1093/nar/gkl868. Epub 2006 Dec 19.
2
Interplay of circadian clocks and metabolic rhythms.生物钟与代谢节律的相互作用。
Annu Rev Genet. 2006;40:409-48. doi: 10.1146/annurev.genet.40.110405.090603.
3
Molecular components of the mammalian circadian clock.哺乳动物生物钟的分子组成部分。
脊椎动物生物钟相关的 Period 基因的功能和调控多样化。
G3 (Bethesda). 2024 Oct 7;14(10). doi: 10.1093/g3journal/jkae162.
4
PAS Dimerization at the Nexus of the Mammalian Circadian Clock.PAS 二聚体在哺乳动物生物钟的交汇点。
J Mol Biol. 2024 Feb 1;436(3):168341. doi: 10.1016/j.jmb.2023.168341. Epub 2023 Nov 2.
5
Cooperation between bHLH transcription factors and histones for DNA access.bHLH 转录因子与组蛋白在 DNA 获得中的合作
Nature. 2023 Jul;619(7969):385-393. doi: 10.1038/s41586-023-06282-3. Epub 2023 Jul 5.
6
Partial-Methylated HeyL Promoter Predicts the Severe Illness in Egyptian COVID-19 Patients.部分甲基化 HeyL 启动子预测埃及 COVID-19 患者的重症疾病。
Dis Markers. 2022 May 31;2022:6780710. doi: 10.1155/2022/6780710. eCollection 2022.
7
Aging disrupts the temporal organization of antioxidant defenses in the heart of male rats and phase shifts circadian rhythms of systolic blood pressure.衰老破坏了雄性大鼠心脏中抗氧化防御的时间组织，并使收缩压的昼夜节律发生相变。
Biogerontology. 2021 Dec;22(6):603-621. doi: 10.1007/s10522-021-09938-7. Epub 2021 Sep 23.
8
Mechanisms of Binding Specificity among bHLH Transcription Factors.bHLH 转录因子结合特异性的机制。
Int J Mol Sci. 2021 Aug 24;22(17):9150. doi: 10.3390/ijms22179150.
9
The core circadian component, Bmal1, is maintained in the pineal gland of old killifish brain.核心昼夜节律成分Bmal1在老年鳉鱼脑的松果体中得以维持。
iScience. 2020 Dec 9;24(1):101905. doi: 10.1016/j.isci.2020.101905. eCollection 2021 Jan 22.
10
CLOCK-BMAL1 regulates circadian oscillation of ventricular arrhythmias in failing hearts through β1 adrenergic receptor.CLOCK-BMAL1通过β1肾上腺素能受体调节衰竭心脏中室性心律失常的昼夜节律振荡。
Am J Transl Res. 2020 Oct 15;12(10):6122-6135. eCollection 2020.
Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R271-7. doi: 10.1093/hmg/ddl207.
4
The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks.体外实时振荡监测系统可识别生物钟的潜在同步因素。
BMC Mol Biol. 2006 Feb 16;7:5. doi: 10.1186/1471-2199-7-5.
5
Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions.节律性的CLOCK-BMAL1与多个E-box基序结合驱动昼夜节律性Dbp转录和染色质转变。
Nat Genet. 2006 Mar;38(3):369-74. doi: 10.1038/ng1738. Epub 2006 Feb 12.
6
Molecular mechanism of cell-autonomous circadian gene expression of Period2, a crucial regulator of the mammalian circadian clock.Period2（哺乳动物生物钟的关键调节因子）细胞自主昼夜节律基因表达的分子机制。
Mol Biol Cell. 2006 Feb;17(2):555-65. doi: 10.1091/mbc.e05-05-0396. Epub 2005 Nov 9.
7
The daily rhythms of genes, cells and organs. Biological clocks and circadian timing in cells.基因、细胞和器官的每日节律。细胞中的生物钟与昼夜节律。
EMBO Rep. 2005 Jul;6 Spec No(Suppl 1):S9-13. doi: 10.1038/sj.embor.7400424.
8
Circadian rhythms from multiple oscillators: lessons from diverse organisms.来自多个振荡器的昼夜节律：来自不同生物体的经验教训。
Nat Rev Genet. 2005 Jul;6(7):544-56. doi: 10.1038/nrg1633.
9
The orphan nuclear receptor RORalpha regulates circadian transcription of the mammalian core-clock Bmal1.孤儿核受体RORα调节哺乳动物核心生物钟基因Bmal1的昼夜节律转录。
Nat Struct Mol Biol. 2005 May;12(5):441-8. doi: 10.1038/nsmb925. Epub 2005 Apr 10.
10
A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo.一个非典型E盒增强子在体内驱动小鼠Period2昼夜节律振荡。
Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2608-13. doi: 10.1073/pnas.0409763102. Epub 2005 Feb 7.