Name: how transcription activators turn genes on
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 2 min 42 s
Channel: JoVE

転写活性化因子は、RNAポリメラーゼが転写を開始するのを可能にする役割を担うタンパク質です。それらには、DNAに結合するドメインと転写を活性化するドメインの2つの重要なドメインがあります。
DNA結合ドメインには、ヘリックスターンヘリックス、ジンクフィンガー、ロイシンジッパー構造などの一般的なモチーフを含む、いくつかの特徴的な構造モチーフの1つが含まれています。 
ヘリックス・ターン・ヘリックス・ドメインは、ターンを表すアミノ酸鎖によって結合された2つのアルファヘリックスで構成されています。1つのらせんはDNA配列を認識する役割を担い、主要な溝に収まります。これらのタンパク質は二量体としてDNAに結合します。 
亜鉛フィンガーには、アルファヘリックスと、亜鉛原子によって一緒に保持された2本鎖ベータシートが含まれています。らせんは、アミノ酸鎖の2つのヒスティジンの助けを借りて主要な溝に結合します。 
ロイシンジッパーは、DNAに結合するY字型に相互作用する2つのモノマーで構成されています。モノマーは、C末端の7番目の位置ごとにロイシンで構成されており、反対側のモノマー上のロイシンと相互作用します。塩基性モチーフからなるモノマーのN末端はDNAに結合します。
アクチベーターのもう1つの必須ドメインである転写活性化ドメインは、アクチベーターのRNAポリメラーゼへの結合を媒介する必須タンパク質であるコアクチベーターをリクルートします。これらのコアクチベーターは、ヒストン修飾などのいくつかのメカニズムを通じて転写を促進し、その結果、転写機構のDNAへのアクセスが増加します。 
アクチベーターは、コアクチベーターを介してシグナルを送信し、RNAポリメラーゼを活性化して転写を開始することもできます。
場合によっては、活性化剤が転写産物の伸長に不可欠です。一部のポリメラーゼは、数ヌクレオチドの後に転写を一時停止し、転写を再開するために活性化因子の存在を必要とします。 
単一の遺伝子の転写は、いくつかの異なる活性化因子によって調節できます。転写の制御に複数の活性化因子が関与している場合、それらは相乗的に作用して、個々の活性化因子と比較して転写速度を劇的に増加させることができます。

<ol>
	<li>馬、J.(2006)。転写活性化因子と活性化メカニズム。遺伝子発現と調節 (pp. 147-158).スプリンガー、ニューヨーク、ニューヨーク。</li>
	<li>グリーン、MR(2005)。真核生物の転写活性化:まさに的中。分子細胞, 18(4), 399-402.</li>
</ol>

真核生物の転写活性化因子

Eukaryotic Transcription Activators

転写活性化因子は、DNAからRNAへの遺伝子の転写を促進するタンパク質です。 ほとんどの場合、これらのタンパク質には2つの別個のドメインが含まれています。1つはDNAに結合するドメイン、もう1つは転写を活性化するドメインです。ただし、グルココルチコイド受容体や MyoDに見られるように、場合によっては、単一のドメインが結合と転写の活性化の両方に関与しています。

結合ドメインは、DNA上の調節配列を認識し、相互作用することができます。これらのドメインはさまざまなファミリーに分類され、DNAの認識と結合を可能にする構造的特徴に従って名前が付けられます。結合ドメインの一般的なタイプには、ロイシン ジッパー、ジンクフィンガー、ヘリックスターンヘリックスモチーフなどがあります。対照的に、遺伝子転写の活性化を担うドメインは通常、短く単純な配列であり、結合ドメインほど複雑ではありません。 アミノ酸組成によって、グルタミンが豊富、プロリンが豊富、アラニンが豊富などのカテゴリに分類されます。

転写アクチベーターは、一般的な転写因子、RNAポリメラーゼ、コアクチベーターなど、転写に必要なさまざまなタンパク質の動員を助けます。これらすべてのタンパク質は一緒になって開始前複合体として知られており、適切な位置への動員は転写活性化因子に依存しています。 これらのアクチベーターは、遺伝子のプロモーターに近い部位、または遺伝子から数千塩基対離れた部位に結合して機能を実行します。 遺伝子から離れた部位に結合している場合、DNAの柔軟性を利用して、それらを曲げて遺伝子プロモーターに近づけます。転写活性化因子は、転写プロセスが途中で停止した場合に転写の伸長を継続したり、転写を再開したりするためにも必要です。 転写活性化因子は相乗的に作用することが知られています。 複数のアクチベーターの作用によって達成される転写は、個別に作用する個々の因子の合計として起こるものよりも高くなります。

他のタンパク質と同様に、転写活性化因子は転写後修飾を受けます。 多くの場合、これらの修飾は転写の正の制御に役立ちます。たとえば、腫瘍抑制に関与する遺伝子を制御する活性化因子であるp53をアセチル化すると、DNAへの結合能力が増加します。

転写活性化因子は、DNAからRNAへの遺伝子の転写を促進するタンパク質です。ほとんどの場合、これらのタンパク質には2つの別々のドメインが含まれています...

Education

JoVE Core

Molecular Biology

分子生物学

Unit 1

ユニット1

Gene Expression

遺伝子発現

KEY TERMS AND CONCEPTS

主要用語と概念

how transcription activators turn genes on

Transcription activators are proteins that help turn genes on by promoting transcription from DNA to RNA. They often have two parts. One part binds to DNA, and the other part activates transcription. In some proteins, such as the glucocorticoid receptor and MyoD, one domain can do both jobs.

The DNA-binding part recognizes specific regulatory sequences on the DNA. These binding domains are grouped into families based on their structure. Common examples include the leucine zipper, zinc finger, and helix-turn-helix motifs. The activation part is usually shorter and simpler. It is often described by amino acid content, such as glutamine-rich, proline-rich, or alanine-rich sequences.

Transcription activators also help recruit the proteins needed to start transcription. These include general transcription factors, RNA polymerase, and co-activators. Together, these proteins form the pre-initiation complex. Activators can bind near a gene promoter or thousands of base pairs away. When they bind far away, DNA bending helps bring them close to the promoter.

These proteins can also help transcription continue if it pauses partway through or needs to start again. Many activators work synergistically, which means several together can produce more transcription than each one alone. Like other proteins, activators can be modified after they are made. For example, acetylation of p53 increases its ability to bind DNA and helps regulate genes involved in tumor suppression.

How Transcription Activators Turn Genes On

how-transcription-activators-turn-genes-on

cell specific gene expression

How Cells Switch Genes On and Off

Cells switch genes on and off to make different proteins for different jobs. In multicellular organisms, many cell types are built from the same DNA, but they do not use the same genes in the same way. This difference in gene expression helps explain why cells can look and act so differently. Liver cells are a clear example. They help detoxify blood, make bile to help digest fats, and produce proteins needed for metabolism. To do these jobs, liver cells must express a specific set of genes.

regulation of expression occurs at multiple steps

regulation-of-expression-occurs-at-multiple-steps

How Cells Control Gene Expression

Cells control gene expression at several points between DNA and protein. The most common control point is transcription. At this stage, proteins bind to short regulatory DNA sequences and can either increase or reduce transcription of the linked gene. After transcription, a precursor mRNA is made. This pre-mRNA contains exons, which code for protein, and introns, which do not. It must be processed before translation, and splicing removes the introns and joins the exons. Cells can also regulate...

cis-regulatory sequences

How Cis-Regulatory DNA Controls Transcription

Cis-regulatory sequences are short, non-coding DNA segments that control gene transcription. They sit on the same chromosome as the genes they regulate and act as binding sites for transcriptional regulators. In eukaryotes, these proteins help control gene expression patterns in different cell types. These DNA sequences can be close to a gene or thousands of bases away. When they are far from the gene in the DNA sequence, they are often brought close together in space because chromosomes are...

cooperative binding of transcription regulators

cooperative-binding-of-transcription-regulators

How Transcription Factors Bind DNA

Transcriptional regulators bind to cis-regulatory DNA sequences to control gene transcription. These DNA sequences are very short, usually fewer than ten nucleotide pairs long. Because they are so short, the same sequence can appear by chance in many places across the genome. Some regulators can also bind to groups of similar sequences. That raises the chance of random binding even more. To lower this risk, transcription regulators often form dimers, which are pairs of proteins that bind a DNA...

prokaryotic transcriptional activators and repressors

prokaryotic-transcriptional-activators-and-repressors

Operon Control by Activators and Repressors

Operon control in prokaryotes depends on activators and repressors. Prokaryotic genes are often arranged in groups, not one by one like in eukaryotes. Genes that help carry out the same biochemical process are placed together with their regulatory elements. This group is called an operon, and it is transcribed into a single polycistronic mRNA strand. Activators and repressors are DNA-binding proteins that control transcription in an operon. Activators bind near the promoter, which is the site...

operons

Operons in Bacterial Gene Control

Operons help bacteria control groups of genes at the same time. An operon is a set of genes that are regulated together and can be turned on or off as a unit. This shared control helps bacteria respond quickly to changes in their environment. In many operons, a promoter gives RNA polymerase a place to bind and start transcription. The operon also includes a regulatory region that helps control whether the genes are expressed. When conditions change, the cell can use this setup to manage gene...

the eukaryotic promoter region

Eukaryotic Promoter Motifs and Gene Control

The eukaryotic promoter region is a stretch of DNA located upstream of a gene. It includes an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. These DNA signals help control when transcription begins. The promoter can be divided into proximal and distal regions. The proximal promoter lies close to the gene and includes cis-regulatory sequences and the core promoter. The core promoter is the RNA polymerase binding site, and it is usually found...

co-activators and co-repressors

Chromatin Control in Gene Transcription

Chromatin control plays a major role in gene transcription in eukaryotes. Gene expression is regulated by several proteins that work together at a gene regulatory site. Some of these proteins bind directly to specific DNA sequences, while co-regulators attach to those regulators but do not bind DNA on their own. Co-regulators can act as co-activators or co-repressors, depending on the complex they join. One co-regulator may even switch roles in different settings. For example, the...

eukaryotic transcription activators

Transcription activators are proteins that help turn genes on by promoting transcription from DNA to RNA. They often have two parts. One part binds to DNA, and the other part activates transcription. In some proteins, such as the glucocorticoid receptor and MyoD, one domain can do both jobs. The DNA-binding part recognizes specific regulatory sequences on the DNA. These binding domains are grouped into families based on their structure. Common examples include the leucine zipper, zinc finger,...

eukaryotic transcription inhibitors

How Eukaryotic Gene Repressors Work

Eukaryotic gene repressors help turn specific genes off when the cell needs to control growth, development, or other biochemical processes. These DNA-binding proteins regulate gene expression in eukaryotes. Their presence at the right time and place can be triggered by hormones and signals from other cells. Most transcription inhibitors have two main parts. One part binds DNA, and the other is a repressor domain, which helps shut down transcription. Repressor domains can connect with basal...

combinatorial gene control

Gene Expression by Transcription Factor Combinations

Gene expression can depend on combinations of transcription factors working together. In combinatorial gene control, several transcription factors act in a coordinated way to regulate a single gene. If one or more of these factors are missing, the level of gene expression or repression can change a lot. This kind of control helps explain how a relatively small number of transcription factors can regulate a very large number of genes. More than 30,000 genes are controlled by about 2,000 to...

induced pluripotent stem cells

Reprogramming Cells into Stem Cells

Induced pluripotent stem cells are created by reprogramming mature cells back into a stem-cell state. This process shows that specialized cells can be changed into cells with broader developmental potential. The topic is important in biology because it links cell identity, gene control, and stem cell research. These cells begin as ordinary body cells and are pushed to de-differentiate, or lose their specialized features. After reprogramming, they behave like pluripotent stem cells, which means...

master transcription regulators

MEF2C and Gene Control Cascades

MEF2C is a master transcription regulator that controls gene expression in coordinated cascades. These regulators are proteins that manage the activity of multiple genes that often work together to produce a complex outcome. When a master transcription regulator is activated, it can start a chain of transcriptional activation that supports that outcome. Master transcription regulators can act in two main ways. They may bind directly to the regulatory sequences of several genes involved in a...

epigenetic regulation

DNA Methylation and Histone Changes

Epigenetic regulation controls gene activity without changing the DNA sequence. It helps determine when genes are turned on or off in a cell. Two major epigenetic mechanisms are DNA methylation and histone modification. DNA methylation adds chemical groups to DNA, while histone changes affect how tightly DNA is packed around histone proteins. These changes can make genes easier or harder to use. In high school biology, epigenetic regulation is important for understanding how cells with the...

genomic imprinting and inheritance

Genomic Imprinting in Human Disease

Genomic imprinting affects how some inherited genes are turned on or off in human cells. Diploid organisms inherit chromosomes from both parents, and each gene usually has two alleles. In most cases, both alleles are expressed. If one allele is missing or mutated, the other can often compensate, but some genes do not work that way. In genomic imprinting, a gene or its regulatory sequence carries chemical tags, such as methyl groups, on the copy inherited from only one parent. These tags are...

key terms and concepts

Learn how transcription activators bind DNA, recruit the pre-initiation complex, and boost gene transcription with examples like p53, MyoD, and the glucocorticoid receptor.

How Transcription Activators Turn Genes On | JoVE K12

molecular biology

JoVE Core 分子生物学は、明確で簡潔なアニメーション ビデオ レッスンを通じて細胞の分子プロセスを紹介します。さらに、科学者の実際のビデオでは、これらの概念の応用が現代の研究室での実際の実験を通じて実証されています。

How Transcription Activators Turn Genes On

Description

Transcript

Tags