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

Les activateurs transcriptionnels sont des protéines qui permettent à l'ARN polymérase d'initier la transcription. Ils ont deux domaines essentiels, un qui se lie à l'ADN et un autre qui active la transcription. Les domaines de liaison à l'ADN contiennent l'un des motifs structurels caractéristiques, y compris les motifs communs, comme les structures hélice-coude-hélice, doigt de zinc et glissière à leucine.Un domaine hélice-coude-hélice est composé de deux hélices alpha regroupées par une chaîne d'acides aminés qui représente le tour. Une hélice est responsable de la reconnaissance de la séquence d'ADN et s'insère dans la rainure principale. Ces protéines se lient à l'ADN en tant que dimères.Un doigt de zinc contient une hélice alpha et un feuillet bêta à deux brins, maintenus ensemble par un atome de zinc. L'hélice se lie à la rainure principale à l'aide de deux histidines et de sa chaîne d'acides aminés. Une glissière à leucine est composée de deux monomères qui interagissent l'un avec l'autre sous la forme d'un Y qui se lie à l'ADN.Les monomères se composent de leucine à chaque septième position à l'extrémité C-terminale, qui interagit avec la leucine sur le monomère opposé. Le N-terminal du monomère, qui est composé de motifs de base, se lie à l'ADN. L'autre domaine essentiel de l'activateur, le domaine d'activation de la transcription, recrute les coactivateurs, protéines essentielles qui médient la liaison des activateurs à l'ARN polymérase.Ces coactivateurs favorisent la transcription par le biais de plusieurs mécanismes, tels que la modification des histones, qui se traduit par un accès accru de la machinerie transcriptionnelle à l'ADN. Les activateurs peuvent aussi envoyer des signaux via leurs coactivateurs pour activer l'ARN polymérase et lancer la transcription. Dans certains cas, les activateurs sont essentiels à l'élongation de la transcription.Certaines polymérases interrompent la transcription après quelques nucléotides et ont besoin de la présence d'un activateur pour redémarrer la transcription. La transcription d'un seul gène peut être régulée par plusieurs activateurs différents. Lorsque plus d'un activateur est impliqué dans la régulation de la transcription, ils peuvent agir en synergie pour augmenter considérablement le taux de transcription par rapport à celui des activateurs individuels.

<ol>
	<li>Ma, J. (2006). Activateurs transcriptionnels et mécanismes d’activation. Dans Expression et régulation des gènes (pp. 147-158). Springer, New York, État de New York.</li>
	<li>Green, M. R. (2005). Activation de la transcription eucaryote : en plein dans la cible. Cellule moléculaire, 18(4), 399-402.</li>
</ol>

activateurs de transcription eucaryotes

Eukaryotic Transcription Activators

Les activateurs de transcription sont des protéines qui favorisent la transcription des gènes de l'ADN à l'ARN. Dans la plupart des cas, ces protéines contiennent deux domaines distincts : un domaine qui se lie à l'ADN et un domaine qui active la transcription ; cependant, dans certains cas, un seul domaine est responsable à la fois de la liaison et de l'activation de la transcription, comme on le voit dans le récepteur des glucocorticoïdes et MyoD.

Les domaines de liaison sont capables de reconnaître et d'interagir avec les séquences régulatrices de l'ADN. Ces domaines sont classés en différentes familles et nommés en fonction des caractéristiques structurelles qui permettent la reconnaissance et la liaison de l'ADN. Certains types courants de domaines de liaison incluent les motifs de fermeture à glissière de leucine, de doigt de zinc et d'hélice-tour-hélice. En revanche, les domaines responsables de l’activation de la transcription génique sont généralement des séquences courtes et simples et sont moins complexes que les domaines de liaison. Ils sont classés selon leur composition en acides aminés en catégories, telles que riches en glutamine, riches en proline et riches en alanine.

Les activateurs de transcription aident au recrutement de diverses protéines nécessaires à la transcription, telles que les facteurs de transcription généraux, l'ARN polymérase et les co-activateurs. Toutes ces protéines réunies sont connues sous le nom de complexe de pré-initiation et dépendent des activateurs de transcription pour leur recrutement à l'emplacement approprié. Ces activateurs peuvent se lier à un site proche du promoteur du gène ou à plusieurs milliers de paires de bases éloignés du gène pour remplir leur fonction. Dans les cas où ils sont liés à un site éloigné du gène, ils comptent sur la flexibilité de l’ADN pour se plier et les rapprocher du promoteur du gène. Les activateurs de transcription sont également nécessaires pour poursuivre l’allongement d’une transcription ou la réinitiation de la transcription dans les cas où le processus s’arrête à mi-chemin. Les activateurs de transcription sont connus pour agir en synergie. La transcription obtenue par l’action de plusieurs activateurs est supérieure à ce qui se produirait en tant que somme de facteurs individuels travaillant séparément.

Comme les autres protéines, les activateurs de transcription sont sujets à des modifications post-transcriptionnelles. Dans de nombreux cas, ces modifications contribuent à une régulation positive de la transcription. Par exemple, l'acétylation de p53, un activateur qui régule les gènes responsables de la suppression des tumeurs, augmente sa capacité à se lier à l'ADN.

Activateurs de transcription eucaryotes

Les activateurs de transcription sont des protéines qui favorisent la transcription des gènes de l’ADN à l’ARN. Dans la plupart des cas, ces protéines contiennent deux domaines distincts...

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Gene Expression

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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 Biologie Moléculaire illustre les processus moléculaires au sein de la cellule grâce à des leçons vidéos claires et concises. Les applications de ces concepts sont ensuite démontrées grâce à des expériences concrètes en laboratoire.

How Transcription Activators Turn Genes On

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