Name: chromatin control in gene transcription
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 2 min 4 s
Channel: JoVE

전사는 DNA에 결합하는 단백질인 활성제(activator)와 억제자(repressor)에 의해 조절됩니다. 진핵생물에서 이러한 조절 단백질은 종종 제대로 기능하기 위해 공동 조절자(co-regulator)라고 하는 추가 단백질을 필요로 합니다.
이러한 co-regulator는 activator 또는 repressor complex에 결합하지만, DNA에 직접 결합할 수 없기 때문에 cis-regulatory sequence를 인식하지 못합니다. 
전사 조절인자는 co-regulator가 연관되기 전에 cis-regulatory sequence에 결합하며, regulator와 co-regulator는 조절자가 DNA에 결합되지 않는 한 안정적인 복합체를 형성할 수 없는 경우가 많습니다. 어떤 경우에는 RNA 분자가 복합체의 모든 단백질을 함께 유지하는 골격 역할도 합니다.
이러한 공동 조절자 중 일부는 히스톤 아세틸전이효소 및 탈아세틸화효소와 같은 유전자 발현을 조절할 수 있는 효소입니다.
아세틸전이효소(Acetyltransferase)는 아세틸기를 히스톤으로 전달하여 DNA를 느슨하게 하고 전사를 촉진하는 공동 활성제입니다. 탈아세틸화효소는 아세틸기를 제거하는 공동 억제제(co-repressor)로, 히스톤 주위에 DNA를 단단히 포장하고 전사를 방지합니다.
예를 들어, 공동 조절자인 SMRT는 양성 호르몬 반응 요소에서 갑상선 호르몬 수용체와 연관되어 기저 전사를 억제하는 공동 억제자로 작용합니다. 호르몬이 수용체에 결합하면 SMRT가 해리되고 공동 활성화제가 결합하여 전사를 활성화합니다. 
그러나 음성 호르몬 반응 요소의 동일한 수용체에 결합하면 SMRT는 호르몬이 없을 때 전사를 활성화합니다. 따라서 공동 활성제 역할을 합니다.

<ol>
	<li>Lee, J. W., Cheong, J., Lee, Y. C., Na, S. Y., & Lee, S. K. (2000). 핵 수용체 작용의 분자 메커니즘 해부 : 전사 공동 활성제 및 코어 프레서. 실험 및 분자 의학, 32(2), 53-60.</li>
	<li>Gao, Z., Chiao, P., Zhang, X., Zhang, X., Lazar, M.A., Seto, E., ... & 예, J. (2005). IκBα 유전자 프로모터에서 NF-κB의 공동 활성제 및 코어프레서. 생물 화학 저널, 280 (22), 21091-21098.</li>
	<li>Purcell, D. J., Jeong, K. W., Bittencourt, D., Gerke, D. S., & Stallcup, M. R. (2011). 전사 조절에서 히스톤 메틸전이효소 G9a에 의한 공동 활성제 대 코어프레서 기능에 대한 뚜렷한 메커니즘. 생물 화학 저널, 286(49), 41963-41971.</li>
</ol>

공동 활성화제 및 공동 억제인자

Co-activators and Co-repressors

유전자 전사는 유전자 조절 부위에서 복합체를 형성하는 여러 단백질의 시너지 작용에 의해 조절됩니다. 이는 유전자 발현 조절이 복잡한 과정인 진핵생물에서 관찰됩니다. 진핵생물의 조절 단백질은 크게 두 가지 유형으로 분류될 수 있습니다. 즉, 특정 DNA 서열에 직접 결합하는 조절 인자와 조절 단백질과 결합하지만 DNA에 직접 결합할 수 없는 공동 조절 인자입니다. 이러한 공동 조절자는 기능에 따라 공동 활성자 또는 공동 억제인자로 더 나뉩니다.

개별 공동 조절자는 연관된 복합체에서의 역할에 따라 공동 활성자 또는 공동 억제인자로 기능할 수 있습니다. 예를 들어, 전사 공동억제인자 G9a는 GRIP1 및 CARM1과 같은 다른 공동 활성화제와 함께 스테로이드 호르몬 수용체에 대한 유전자 발현의 활성화에 참여합니다. 단백질의 개별 도메인은 이러한 다양한 기능을 수행합니다. 복합체에서의 역할 외에도 이러한 조절인자는 염색질 구조의 리모델링을 통해 유전자 발현을 조절하는 데 도움을 줄 수 있는 효소 활성을 가지고 있습니다.

히스톤 아세틸트랜스퍼라제와 히스톤 데메틸라제는 공동 활성화제로 기능합니다. 그러나 이러한 기능을 수행하려면 먼저 전사 활성화제에 의해 조절 부위에 국한되어야 합니다. 히스톤 아세틸트랜스퍼라제는 히스톤 꼬리의 라이신 잔기를 아세틸화할 수 있습니다. 아세틸화는 염색질을 풀고 유전자 발현을 촉진합니다. 반면, 히스톤 데아세틸라제와 히스톤 메틸트랜스퍼라제는 보조억제자로 기능합니다. 이러한 변형은 모두 염색질 구조를 강화하여 유전자 발현을 방지합니다.

유전자 전사는 유전자 조절 부위에서 복합체를 형성하는 여러 단백질의 시너지 작용에 의해 조절됩니다. 이것은 다음에서 관찰됩니다 ...

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 1

제1단원

Gene Expression

유전자 발현

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 transcriptional co-repressor G9a helps activate a steroid hormone receptor gene with co-activators such as GRIP1 and CARM1. Different protein domains help carry out these different jobs.

Many of these regulators also have enzyme activity that changes chromatin structure. Histone acetyltransferases and histone demethylases act as co-activators, but they must first be brought to the regulatory site by a transcription activator. Histone acetyltransferases add acetyl groups to lysine residues on histone tails, which loosens chromatin and supports gene expression.

Other enzymes act as co-repressors. Histone deacetylases and histone methyltransferases tighten chromatin structure and reduce gene expression. These chromatin changes help explain how co-regulators can either turn genes on or keep them off.

Chromatin Control in Gene Transcription

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 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 co-regulators change chromatin to turn genes on or off, including histone acetylation, deacetylation, and methylation in eukaryotes.

Chromatin Control in Gene Transcription | 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.

Chromatin Control in Gene Transcription

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