Name: how eukaryotic gene repressors work
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 1 min 52 s
Channel: JoVE

전사 억제제는 유전자의 전사를 억제할 수 있습니다. 그들은 DNA의 조절 서열에 결합하는 뚜렷한 도메인과 전사를 억제하는 또 다른 도메인을 가지고 있습니다.
이 단백질은 다양한 메커니즘을 통해 전사를 억제할 수 있습니다. 가장 간단한 방법은 여러 가지 메커니즘 중 하나를 통해 활성제가 시스 조절 서열에 결합하는 것을 차단하는 것입니다.
어떤 경우에는 억제제가 조절 서열에 경쟁적으로 결합하여 활성제의 결합을 방지합니다. 다른 경우, 억제제는 활성제 결합 부위 근처의 부위에 결합하고, 억제자 도메인은 활성제와 상호 작용하여 조절 서열에 결합하는 것을 방지합니다. 
억제제는 DNA의 일반 전사 인자의 결합 부위에 경쟁적으로 결합하고 전사 기계의 조립을 차단할 수도 있습니다.
억제제는 또한 자체 억제성 시스 조절 서열에 결합할 수 있으며, 이는 조절 영역에 활성제가 있는 경우에도 전사 개시를 방지할 수 있습니다.
전사 억제제가 사용하는 가장 일반적인 메커니즘 중 하나는 억제자 도메인을 사용하여 공동 억제자로 알려진 단백질을 모집하는 것입니다. 공동 억제인자는 종종 전사를 억제할 수 있는 효소 활성을 가지고 있습니다. 
많은 공동 억제자는 히스톤 탈아세틸화효소, 히스톤 메틸전이효소 및 기타 염색질 재생효소로 기능합니다. 이러한 변형은 뉴클레오솜에서 DNA의 단단한 패킹을 초래하고 전사 인자와 중합효소가 조절 부위에 접근하는 것을 제한하여 전사를 억제합니다.

<ol>
	<li>Lodish H, Berk A, Zipursky SL, et al. 분자 세포 생물학.4판. 뉴욕: W. H. 프리먼; 2000. 섹션 10.7, 진핵 생물 전사 조절의 분자 메커니즘. 제공 제품: https://www.ncbi.nlm.nih.gov/books/NBK21677/</li>
	<li>Hanna-Rose, W., & Hansen, U. (1996). 진핵생물 전사 억제자의 능동적 억제 메커니즘. 유전학 동향, 12(6), 229–234. 도:10.1016/0168-9525(96)10022-6</li>
	<li>렌카위츠, R. (1990). 진핵생물의 전사 억제(transcriptional repression in eukaryotes). 유전학 동향, 6, 192–196. 도이 : 10.1016 / 0168-9525 (90) 90176-7</li>
</ol>

진핵생물 전사 억제제

Eukaryotic Transcription Inhibitors

배아 발달 및 세포 성장 조절과 같은 특정 생화학적 과정은 특정 유전자의 억제에 따라 달라집니다. 진핵생물 전사 억제제로 알려진 DNA 결합 단백질은 진핵생물의 유전자 발현 억제를 조절합니다. 세포에서 필요한 위치와 시간에 이러한 억제제가 존재하는 것은 호르몬의 존재와 다른 세포의 추가 신호에 의해 촉발됩니다.

진핵생물의 전사 억제제는 일반적으로 DNA 결합 도메인과 억제 도메인이라는 두 개의 서로 다른 도메인을 포함합니다. 전사 억제제의 억제 도메인은 기본 전사 조절 인자, 활성 인자, 보조 활성 인자 및 보조 억제 인자와 같은 다른 단백질에 결합할 수 있습니다. 억제 도메인은 알라닌이 풍부한 도메인, 글루타민이 풍부한 도메인, 프롤린이 풍부한 도메인과 같이 구성 아미노산을 기준으로 모호하게 분류될 수 있습니다. 또한 산성 또는 염기성 도메인으로 분류할 수도 있고, 친수성 또는 소수성 도메인으로 분류할 수도 있습니다. 이 도메인은 종종 상호교환이 가능하며, 서로 다른 억제 도메인이 동일한 DNA 결합 도메인과 연관될 수 있습니다.

진핵생물 전사 억제제는 DNA 결합 억제, 활성화 차단, 유전자 침묵이라는 세 가지 주요 메커니즘을 통해 기능을 수행할 수 있습니다.

DNA 결합의 억제는 활성제가 프로모터 또는 인핸서 부위에 결합하는 것을 방지하거나, 전사 개시 복합체가 전사 시작 부위 또는 TATA 박스에 결합하는 것을 방지할 수 있습니다. 이는 조절 또는 시작 부위에 대한 억제제의 결합을 통해 또는 억제 도메인과 활성화제, 보조 활성화제 또는 전사 기계에 관련된 단백질의 결합을 통해 발생할 수 있습니다. 예를 들어, 인간의 경우 전사 억제제 NF-E는 태아 γ-글로빈 유전자의 CCAAT 상자에 결합하여 활성화 인자 CP1의 결합을 억제합니다.

활성화를 차단하면 프로모터나 인핸서에 결합된 전사 활성제의 신호가 전사 시작 부위에 도달하는 것을 방지할 수 있습니다. 이는 억제제 myc-PRF가 프로모터 옆에 결합하는 c-myc의 조절과 같이 억제제가 프로모터 또는 인핸서에 인접한 부위에 결합할 때 발생할 수 있습니다. 이는 또한 DNA 결합 활성화제에 대한 억제제 결합을 통해 발생할 수도 있습니다. 이러한 유형의 억제는 효모의 억제제 GAL80이 프로모터에 결합될 때 활성화인자 GAL4에 결합할 때 발생합니다.

유전자 침묵은 억제제가 기구를 구성하는 단백질 중 하나와 전사 시작 부위 근처의 DNA 부위에 동시에 결합하여 전사 개시 복합체를 잠그거나 해체하여 전사 기구를 고정할 때 발생합니다. 예를 들어, 효모에서 억제제 α-2는 활성자 GRM 및 GRM의 결합 부위에 접해 있는 DNA 서열에 이량체로 결합하여 교배 유형 α-특이적 유전자를 비활성화합니다.

배아 발달 및 세포 성장 조절과 같은 특정 생화학적 과정은 특정 유전자의 억제에 의존합니다.DNA 결합 ...

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 1

제1단원

Gene Expression

유전자 발현

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 transcription regulators, activators, co-activators, and co-repressors.

These repression domains are often grouped by their amino acids, such as alanine-rich, glutamine-rich, and proline-rich domains. They can also be described as acidic or basic, and as hydrophilic or hydrophobic. Different repressor domains can often be swapped onto the same DNA-binding domain.

Eukaryotic transcription inhibitors act through three main mechanisms: inhibiting DNA binding, blocking activation, and gene silencing. Inhibiting DNA binding stops an activator from attaching to a promoter or enhancer, or it prevents the transcription initiation complex from binding the transcription start site or the TATA box. This can happen when the inhibitor binds the regulatory site or start site, or when its inhibitory domain interacts with activators, co-activators, or other transcription machinery proteins.

One example is NF-E in humans. It binds the CCAAT box of the fetal gamma-globin gene and blocks the activator CP1 from binding. Blocking activation works differently. The inhibitor can bind next to a promoter or enhancer, as in c-myc regulation, where myc-PRF binds beside the promoter. It can also bind to an activator already attached to DNA. In yeast, GAL80 binds GAL4 when GAL4 is bound to the promoter.

Gene silencing happens when the inhibitor locks or disrupts the transcription initiation complex. It does this by binding both a protein in the machinery and a DNA site near the transcription start site, which anchors the complex. In yeast, the alpha-2 inhibitor works this way to turn off mating type a-specific genes. It binds as a dimer to the activator GRM and to DNA sequences beside the GRM binding site.

How Eukaryotic Gene Repressors Work

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

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

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 eukaryotic gene repressors control transcription through DNA binding, blocking activation, and gene silencing, with clear examples from humans and yeast.

How Eukaryotic Gene Repressors Work | 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 Eukaryotic Gene Repressors Work

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