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

전사 조절인자(transcriptional regulator)는 시스 조절 염기서열(cis-regulatory sequence)로 알려진 DNA의 짧은 염기서열을 인식하고 결합하는 단백질입니다. 이러한 염기서열은 일반적으로 10개 미만의 뉴클레오티드 길이이기 때문에 게놈에서 동일한 염기서열이 무작위로 발생할 가능성이 매우 높습니다.
많은 레귤레이터는 무작위 서열에 대한 결합을 제한하기 위해 이량체 쌍을 형성합니다. 이량체는 10개의 뉴클레오티드보다 긴 염기서열을 결합할 수 있으므로 염기서열이 게놈에 무작위로 존재할 가능성이 줄어들고 결합 특이성이 증가합니다.
이러한 조절 이량체는 동일한 유형의 단량체로 만들어진 동형이량체 또는 다른 유형의 단량체를 가진 이종이량체일 수 있습니다.쌍은 서로 다른 단량체로 구성될 수 있기 때문에 다양한 조합으로 새로운 유형의 단백질이 필요하지 않고 다른 서열에 결합할 수 있습니다.
DNA에 결합하지 않을 때, 협력 조절자는 때때로 약한 비공유 상호작용을 통해 이량체를 형성하는 단량체로 존재하지만, 이러한 구조는 협력 결합으로 인해 DNA에 결합할 때 밀접하게 연결된 이량체를 형성합니다.
협력 결합(Cooperative binding)은 단량체가 시스 조절 서열에 결합하면 구조적 변화로 인해 두 번째 조절 물질 결합의 가능성이 증가하는 현상입니다. 이를 통해 두 번째 조절제가 결합 부위의 다른 쪽에 단단히 결합하고 첫 번째 조절체와 이량체를 형성할 수 있습니다.
이것은 대부분의 경우 특정 시스 조절 서열의 모든 인스턴스가 레귤레이터를 가지고 있거나 그 중 어느 것도 바인딩하지 않음을 의미합니다. 
많은 유전자의 경우, DNA는 히스톤 단백질로 단단히 싸여 있어 전사 조절자가 시스 조절 서열에 접근하는 것을 방지합니다. 그러나 느슨하게 결합된 DNA의 끝은 결합할 수 있는 약간의 공간을 허용합니다. 이 사이트에서 단일 레귤레이터의 결합은 구조를 푸는 데 도움이 될 수 있으므로 다른 레귤레이터가 결합할 수 있습니다.

<ol>
	<li>Alberts et al., 6판; 375, 378-380페이지</li>
	<li>Morgunova, E., & Taipale, J. (2017). 협력 전사 인자 결합의 구조적 관점. 구조 생물학의 현재 의견, 47, 1-8.</li>
</ol>

전사 조절기의 협력적 결합

Cooperative Binding of Transcription Regulators

전사 조절인자는 DNA의 특정 Cis 규제 시퀀스에 결합하여 유전자 전사를 조절합니다. 이러한 Cis 규제 시퀀스는 매우 짧으며 일반적으로 길이가 10개 뉴클레오티드 쌍 미만입니다. 길이가 짧다는 것은 게놈 전체에 걸쳐 정확히 동일한 서열이 무작위로 발생할 확률이 높다는 것을 의미합니다. 조절자는 유사한 서열의 그룹에도 결합할 수 있으므로 무작위 결합 가능성이 더욱 높아집니다. 전사 조절자는 단량체가 결합하는 기간의 두 배만큼 서열에 결합하는 이합체를 형성하여 서열을 증가시키고 무작위 결합 가능성을 줄입니다. 전사 조절 이량체는 동종이량체 또는 이종이량체일 수 있습니다. 용액에서 이러한 협력 조절자는 단량체 또는 약하게 연결된 이량체로 존재합니다. 그러나 이러한 단량체가 DNA의 확장된 Cis 규제 시퀀스에 결합하면 안정적인 이량체를 형성합니다.

협동성은 단량체 단백질의 결합이 DNA의 구조적 변화를 일으키고 다른 단량체에 대한 조절 부위의 친화력을 증가시키는 현상입니다. 이를 통해 단량체가 Cis 규제 시퀀스에서 이량체로 결합할 수 있습니다. 이 현상은 또한 뉴클레오솜의 히스톤 단백질에 단단히 결합되어 있는 DNA에 위치한 위치에 조절자가 접근하는 데 도움이 됩니다. 첫 번째 결합은 일반적으로 뉴클레오솜 끝의 DNA에서 발생하는데, 여기서는 단단히 결합되지 않습니다. 이 부위에 결합하면 DNA가 히스톤에서 멀어지게 되어 뉴클레오솜이 풀립니다. 포장을 풀면 다른 규제 기관에 대한 접근성이 높아집니다. 진핵생물에서 전사 인자 결합은 주로 협동성에 달려 있습니다. 어떤 경우에는 협동성이 발생할 수 있지만 원핵생물에서 전사 조절인자의 결합은 대부분 비협조적입니다. 이러한 경우 조절인자는 여러 비공유 상호작용에 의해 함께 결합된 안정적인 이합체로 존재합니다.

알려지지 않은 조절인자가 협력적으로 결합하는지 또는 비협조적으로 결합하는지 여부는 단백질 농도에 대해 DNA에서 점유된 결합 부위의 수를 표시하여 결정할 수 있습니다. 플롯이 S자형 곡선인 경우 이는 조절기가 결합 부위에 협력적으로 결합함을 나타냅니다. 곡선이 점유된 모든 바인딩 사이트에 접근하면서 수평을 이루기 전에 꾸준히 상승하면 바인딩이 비협조적임을 나타냅니다.

전사 조절인자(transcriptional regulator)는 유전자 전사를 조절하기 위해 DNA의 특정 시스 조절 서열에 결합합니다. 이러한 시스 조절 서열은 ...

cooperative-binding-of-transcription-regulators

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 1

제1단원

Gene Expression

유전자 발현

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 분자생물학은 명확하고 간결한 애니메이션을 통해 분자 단계에서 일어나는 세포 과정을 설명합니다.또한, 과학자가 직접 실험을 진행하는 실사 영상을 통해 분자생물학 개념의 응용 사례를 보여줍니다.

How Transcription Factors Bind DNA

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