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

전사 활성화제(transcription activator)는 RNA 중합효소가 전사를 시작할 수 있도록 하는 단백질입니다. 그들은 DNA에 결합하는 영역과 전사를 활성화하는 두 가지 필수 영역을 가지고 있습니다.
DNA 결합 도메인은 나선-턴-나선(helix-turn-helix), 아연 핑거(zinc finger) 및 류신 지퍼 구조(leucine zipper structure)와 같은 일반적인 모티프를 포함하여 몇 가지 특징적인 구조적 모티프 중 하나를 포함합니다. 
helix-turn-helix domain은 회전을 나타내는 아미노산 사슬로 결합된 두 개의 알파 나선으로 구성됩니다. 하나의 나선은 DNA 염기서열을 인식하는 역할을 하며 주요 홈에 맞습니다. 이 단백질은 이량체로 DNA에 결합합니다. 
아연 손가락은 알파 나선과 아연 원자에 의해 함께 유지되는 두 가닥 베타 시트를 포함합니다. 나선은 아미노산 사슬에 있는 두 개의 히스티딘의 도움으로 주요 홈에 결합합니다. 
류신 지퍼는 DNA에 결합하는 Y 모양으로 서로 상호 작용하는 두 개의 단량체로 구성됩니다. 단량체는 C 말단 말단의 모든 7번째 위치에 류신으로 구성되며, 이는 반대쪽 단량체의 류신과 상호 작용합니다. 기본 모티브로 구성된 단량체의 N-말단은 DNA에 결합합니다.
활성제의 또 다른 필수 도메인인 전사 활성화 도메인(transcription activating domain)은 RNA 중합효소에 대한 활성제의 결합을 매개하는 필수 단백질인 공동 활성제(co-activator)를 모집합니다. 이러한 공동 활성제는 히스톤 변형과 같은 여러 메커니즘을 통해 전사를 촉진하여 DNA에 대한 전사 기계의 접근을 증가시킵니다. 
활성제는 또한 공동 활성제를 통해 신호를 보내 RNA 중합효소를 활성화하고 전사를 시작할 수 있습니다.
어떤 경우에는 활성제가 대본의 연장에 필수적입니다. 일부 중합효소는 몇 개의 뉴클레오티드 후에 전사를 일시 중지하고 전사를 다시 시작하기 위해 활성제의 존재가 필요합니다. 
단일 유전자의 전사는 여러 다른 활성제에 의해 조절될 수 있습니다. 하나 이상의 활성제가 전사 조절에 관여하는 경우, 그들은 시너지 효과를 발휘하여 개별 활성제에 비해 전사 속도를 크게 증가시킬 수 있습니다.

진핵생물 전사 활성화제

Eukaryotic Transcription Activators

전사 활성제는 DNA에서 RNA로의 유전자 전사를 촉진하는 단백질입니다. 대부분의 경우 이러한 단백질은 두 개의 별도 도메인, 즉 DNA에 결합하는 도메인과 전사 활성화를 위한 도메인을 포함합니다. 그러나 어떤 경우에는 글루코코르티코이드 수용체와 MyoD에서 볼 수 있듯이 단일 도메인이 전사의 결합과 활성화를 모두 담당합니다.

결합 도메인은 DNA의 조절 서열을 인식하고 상호작용할 수 있습니다. 이러한 도메인은 DNA 인식 및 결합을 가능하게 하는 구조적 특성에 따라 서로 다른 계열로 분류되고 명명됩니다. 결합 도메인의 일반적인 유형에는 류신 지퍼, 징크 핑거 및 나선-회전-나선 모티프가 포함됩니다. 대조적으로, 유전자 전사 활성화를 담당하는 도메인은 일반적으로 짧고 단순한 서열이며 결합 도메인보다 덜 복잡합니다. 아미노산 구성에 따라 글루타민 풍부, 프롤린 풍부, 알라닌 풍부 등의 카테고리로 분류됩니다.

전사 활성화제는 일반 전사 인자, RNA 폴리머라제, 공동 활성화제 등 전사에 필요한 다양한 단백질의 동원을 돕습니다. 이러한 모든 단백질은 사전 개시 복합체(pre-initiation complex)로 알려져 있으며 적절한 위치로 모집하기 위해 전사 활성화제에 의존합니다. 이러한 활성화제는 유전자의 프로모터에 가까운 부위나 유전자에서 수천 염기쌍 떨어진 부위에 결합하여 기능을 수행할 수 있습니다. 유전자에서 멀리 떨어진 곳에 결합되어 있는 경우, DNA의 유연성에 의존하여 구부려 유전자 프로모터에 근접하게 만듭니다. 전사 활성화제는 과정이 중간에 중단되는 경우 전사의 연장을 계속하거나 전사를 다시 시작하는 데에도 필요합니다. 전사 활성화제는 상승적으로 작용하는 것으로 알려져 있습니다. 여러 활성화제의 작용으로 달성되는 전사는 개별적으로 작동하는 개별 요인의 합으로 발생하는 것보다 높습니다.

다른 단백질과 마찬가지로 전사 활성화제도 전사 후 변형을 겪습니다. 많은 경우 이러한 변형은 전사의 긍정적인 조절에 도움이 됩니다. 예를 들어, 종양 억제에 관여하는 유전자를 조절하는 활성화제인 p53의 아세틸화는 DNA에 결합하는 능력을 증가시킵니다.

전사 활성화제(transcription activator)는 DNA에서 RNA로 유전자의 전사를 촉진하는 단백질입니다. 대부분의 경우, 이러한 단백질은 두 개의 분리된 도메인을 포함합니다 ...

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 1

제1단원

Gene Expression

유전자 발현

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 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 Activators Turn Genes On

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