時計とNPAS2のDNA結合の調節は,NADコファクターのリドックス状態による

J Rutter¹, M Reick, L C Wu

¹Department of Biochemistry, University of Texas-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9152, USA.

Science (New York, N.Y.)

|July 7, 2001

まとめ

シルカディアン・クロックです.

科学分野:

バイオケミストリーバイオケミストリー
分子生物学は分子生物学である.
クロノバイオロジーはクロノバイオロジーを用います.

背景:

昼夜時計は,光,活動,食物によって影響を受け,24時間のサイクルで遺伝子発現を調節します.
Clock:BMAL1とNPAS2:BMAL1は,昼夜リズムを制御する重要な転写因子である.
外部信号と時計の牽引を結びつける正確な分子機構は,完全に理解されていません.

研究の目的:

ニコチナミドアデニン・ディヌクレオチド (NAD) のコファクターが,クロック:BMAL1およびNPAS2:BMAL1ヘテロダイマーのDNA結合活性を調節する役割を調査する.
細胞のリドックス状態が,日中時計の誘導のための媒介者としての可能性を探求する.

主な方法:

クロック:BMAL1およびNPAS2:BMAL1ヘテロジメのDNA結合活性を研究するために,浄化されたシステムを利用しました.
これらの転写因子のDNA結合能力に対するNADコファクターの異なる酸化還元状態の影響を評価した.

主要な成果:

Clock:BMAL1およびNPAS2:BMAL1のDNA結合活動は,NAD共因子の還元酸化状態によって直接調節される.
還元された形式のNAD (NAD(H) とNADP(H)) は,DNA結合を著しく強化する.
酸化された形式のNADは,これらの異体体のDNA結合活動を阻害する.

結論:

NAD共因子によって調節される細胞のリドックス状態は,日中時計のコアコンポーネントのDNA結合機能に直接影響を与えます.
この発見は,食物摂取やニューロンの活動が,直接的なリドックス調節を通して日中の時計に侵入するかもしれないという新しいメカニズムを示唆しています.

さらに関連する動画

10:08

High-Throughput Analysis of Non-Photochemical Quenching in Crops Using Pulse Amplitude Modulated Chlorophyll Fluorometry

Published on: July 6, 2022

14:39

Cholinergic Ligand–dependent Modulation of Oxidative Phosphorylation Coupling in Digitonin-permeabilized BE(2)-C Neuroblastoma Cells

Published on: April 28, 2026

関連する概念動画

02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...

02:19

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,...

01:29

Role of Reduced Coenzymes NADH and FADH₂

The energy released from the breakdown of the chemical bonds within nutrients can be stored either through the reduction of electron carriers or in the bonds of adenosine triphosphate (ATP). In living systems, a small class of compounds functions as mobile electron carriers, molecules that bind to and shuttle high-energy electrons between compounds in pathways. The principal electron carriers that will be considered originate from the B vitamin group and are derivatives of nucleotides; they are...

01:19

Oxidation and Reduction of Organic Molecules

Energy production within a cell involves many coordinated chemical pathways. Most of these pathways are combinations of oxidation and reduction reactions, which occur at the same time. An oxidation reaction strips an electron from an atom in a compound, and the addition of this electron to another compound is a reduction reaction. Because oxidation and reduction usually occur together, these pairs of reactions are called redox reactions.
The removal of an electron from a molecule, results in a...

01:27

Redox Reactions

Redox reactions are vital biochemical processes that underpin energy metabolism in cells. These reactions involve the transfer of electrons between molecules, occurring in tandem as oxidation and reduction. Oxidation refers to the loss of electrons, while reduction denotes their gain. This coupling ensures the seamless flow of electrons through metabolic pathways. For example, in bacterial metabolism, glucose undergoes oxidation to carbon dioxide, while oxygen is simultaneously reduced to...

01:28

Biosynthesis of Nucleic Acids

Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...

関連する実験動画