クリプトクロームは,グルココルチコイド受容体のリズム抑制を媒介する
Katja A Lamia1, Stephanie J Papp, Ruth T Yu
1Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. klamia@scripps.edu
Nature
|December 16, 2011
まとめ
暗号染色体1と2は,体内時計とホルモン反応を調節する. これらのタンパク質の喪失は,グルコースの代謝を乱し,ストレスホルモンのレベルを変化させ,代謝の恒常性におけるそれらの役割を明らかにします.
科学分野:
- クロノバイオロジーはクロノバイオロジーを用います.
- 分子内分泌学 分子内分泌学
- メタボリック・レギュレーション
背景:
- 哺乳類の代謝は強い昼夜リズムを示し,核ホルモン受容体は昼間のサイクルを示している.
- 核ホルモン受容体と日中時計を調整する正確なメカニズムは,ほとんど不明のままです.
研究 の 目的:
- 昼間の共同調節体である暗号クロームとグルココルチコイド受容体との相互作用を解明する.
- クリプトクロームが,グルココルチコイドに対する転写反応にどのように影響し,代謝性ホメオスタシスにどのように影響するのかを理解する.
主な方法:
- クリプトクローム1/2とマウスの胚性線維芽細胞におけるグルココルチコイド受容体間のリガンド依存相互作用を調査した.
- マウスモデルを使用して,遺伝子発現とグルココルチコイドシグナル伝達に対する暗号クローム欠乏の効果を in vivo で分析した.
- クリプトクロームとフォスフェノールピルバートカルボキシキナーゼ1プロモーターのゲノム関連を調べた.
主要な成果:
- クリプトクローム欠乏症は,遺伝子抑制を著しく低下させ,デキサメタゾン誘発の遺伝子発現を増加させ,クリプトクロームがグルココルチコイド受容体の活性化に反対することを示しています.
- クリプトクロームが欠けていたマウスは,グルコース不耐症とコルチコステロンの濃度上昇を示し,下垂体-下垂体-腎上腺軸抑制の障害と肝臓のグルココルチコイドトランザクティベーションの増加を示唆した.
- クリプトクローム1/2は,フォスフェノールピルバートカルボキシキナーゼ1プロモーターと結合することが判明し,デキサメタゾン誘発の転写は,クリプトクローム欠乏性の肝臓において上昇した.
結論:
- 暗号染色体1と2は,日中時計とグルココルチコイド受容体活性との間のメカニズム的なリンクを提供します.
- これらの発見は,ホルモン回路の調節を通じて代謝的恒常性を調節するクリプトクロームの新たな役割を明らかにしています.
関連する概念動画
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
Biological Clocks and Seasonal Responses
The circadian—or biological—clock is an intrinsic, timekeeping, molecular mechanism that allows plants to coordinate physiological activities over 24-hour cycles called circadian rhythms. Photoperiodism is a collective term for the biological responses of plants to variations in the relative lengths of dark and light periods. The period of light-exposure is called the photoperiod.
Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...

