Name: how transcription factors bind dna
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 2 min 13 s
Channel: JoVE

転写調節因子は、シス調節配列として知られるDNAの短い配列を認識して結合するタンパク質です。これらの配列は通常10ヌクレオチド未満であるため、同じ配列がゲノムにランダムに発生する可能性は非常に高いです。
多くの調節因子は、ランダムな配列への結合を制限するために二量体ペアを形成します。二量体は10ヌクレオチドより長い配列に結合できるため、配列がゲノムにランダムに存在する可能性が低くなり、結合特異性が向上します。
これらの調節二量体は、同じタイプのモノマーからなるホモ二量体、または異なるタイプのモノマーを持つヘテロ二量体のいずれかです。ペアは異なるモノマーで構成できるため、さまざまな組み合わせにより、新しいタイプのタンパク質を必要とせずに異なる配列に結合できます。
DNAに結合していないとき、協調的な調節因子はモノマーとして存在し、弱い非共有結合の相互作用を通じて二量体を形成することがありますが、これらの構造は、DNAに結合すると、協力的な結合により密接に結合した二量体を形成します。
協同的結合とは、モノマーがシス制御配列に結合することで、構造変化により第2の調節因子が結合する可能性が高まる現象です。これにより、第2のレギュレーターが結合部位の反対側に強固に結合し、第1のレギュレーターと二量体を形成することができます。
これは、ほとんどの場合、特定のシス調節配列のすべてのインスタンスがレギュレーターを結合しているか、いずれも結合していないことを意味します。 
多くの遺伝子では、DNAはヒストンタンパク質にしっかりと巻き付けられており、転写調節因子がシス調節配列にアクセスするのを防ぎます。ただし、DNAの緩く結合した末端は、結合のためのいくらかのスペースを許容します。この部位に単一の調節因子が結合すると、構造がほどけ、それによって他の調節因子が結合できるようになります。

<ol>
	<li>Alberts et al., 6th edition; pages 375, 378-380</li>
	<li>Morgunova, E., & Taipale, J. (2017).協調転写因子結合の構造的視点構造生物学における現在の意見、47、1-8。</li>
</ol>

転写調節因子の協調的結合

Cooperative Binding of Transcription Regulators

転写調節因子は、DNA内の特定のシス調節配列に結合して遺伝子転写を調節します。これらのシス調節配列は非常に短く、通常は長さが10ヌクレオチド対未満です。 長さが短いということは、ゲノム全体にまったく同じ配列がランダムに存在する可能性が高いことを意味します。調節因子は同様の配列のグループにも結合できるため、ランダムに結合する可能性がさらに高まります。 転写調節因子は、単量体の結合時間の2倍の長さで配列に結合する二量体を形成し、配列を増やしてランダム結合の可能性を減らします。転写調節因子二量体は、ホモ二量体またはヘテロ二量体であり得る。溶液中では、これらの協調的調節因子は単量体または弱く結合した二量体のいずれかとして存在します。しかし、これらの単量体がDNA上の拡張されたシス制御配列に結合すると、安定した二量体を形成します。

協同性とは、単量体タンパク質の結合によってDNAの構造変化が引き起こされ、他の単量体に対する調節部位の親和性が増加する現象です。これにより、単量体がシス制御配列上で二量体として結合することが可能になります。この現象は、調節因子がヌクレオソーム内のヒストンタンパク質に強く結合しているDNA上に位置する、さもなければアクセスできない部位にアクセスするのにも役立ちます。最初の結合は通常、ヌクレオソームの末端にあるDNAで起こり、そこでは強く結合されていません。 この部位で結合すると、DNAがヒストンから離れるようになり、それによってヌクレオソームの開梱が起こります。この開梱により、他の規制サイトへのアクセスが増加します。真核生物では、転写因子の結合は主に協同性に依存します。 場合によっては協力性が生じることもありますが、原核生物における転写調節因子の結合のほとんどは非協力的です。このような場合、調節因子はいくつかの非共有結合性相互作用によって結合された安定な二量体として存在します。

未知の制御因子が協調的に結合するか非協調的に結合するかは、DNA上の占有結合部位の数をタンパク質濃度に対してプロットすることで決定できます。 プロットがS字型の曲線である場合、調節因子が結合部位に協調的に結合していることを示します。曲線が占有されているすべての結合部位に近づくにつれて横ばいになる前に着実に上昇する場合、それは結合が非協力的であることを示します。

転写調節因子は、DNAの特定のシス調節配列に結合して遺伝子転写を調節します。これらのシス調節配列は...

cooperative-binding-of-transcription-regulators

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 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 sequence that is twice as long as the sequence bound by a monomer. These dimers can be homodimers or heterodimers.

In solution, cooperative regulators may exist as monomers or as weakly linked dimers. When they bind to an extended cis-regulatory sequence on DNA, they form stable dimers. Cooperativity means that the binding of one monomer changes the DNA structure and increases the site’s affinity for other monomers. This helps the proteins bind together as dimers on the cis-regulatory sequence.

Cooperativity also helps regulators reach sites on DNA that are tightly wrapped around histone proteins in the nucleosome. These sites are usually hard to access. Binding often starts at the end of the nucleosome, where the DNA is less tightly packed. That first binding step can pull the DNA away from the histones and help unpack the nucleosome, which makes other regulatory sites easier to reach.

In eukaryotes, transcription factor binding depends mainly on cooperativity. In prokaryotes, most transcriptional regulator binding is non-cooperative, although cooperativity can occur in some cases. Non-cooperative regulators are usually stable dimers held together by several non-covalent interactions. The difference can be seen by plotting occupied binding sites against protein concentration. An S-shaped curve suggests cooperative binding, while a steady rise that levels off suggests non-cooperative binding.

How Transcription Factors Bind DNA

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

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

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,...

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 regulators bind cis-regulatory DNA, form dimers, unpack nucleosomes, and how S-shaped curves reveal cooperative binding.

How Transcription Factors Bind DNA | 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 Factors Bind DNA

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