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

La transcription est régulée par des activateurs et des répresseurs, des protéines qui se lient à l’ADN. Chez les eucaryotes, ces protéines régulatrices ont souvent besoin de protéines supplémentaires, appelées corégulateurs, pour fonctionner correctement.
Ces co-régulateurs se lient aux complexes activateurs ou répresseurs, mais ils ne reconnaissent pas les séquences cis-régulatrices, car ils ne peuvent pas se lier directement à l’ADN. 
Un régulateur transcriptionnel se lie à une séquence cis-régulatrice avant que le co-régulateur ne s’associe ; les régulateurs et les co-régulateurs ne peuvent souvent pas former de complexes stables à moins que le régulateur ne soit lié à l’ADN. Dans certains cas, les molécules d’ARN servent également d’échafaudages pour maintenir ensemble toutes les protéines d’un complexe.
Certains de ces corégulateurs sont des enzymes qui peuvent réguler l’expression des gènes, comme les histones acétyltransférases et les désacétylases.
Les acétyltransférases sont des co-activateurs qui transfèrent un groupe acétyle à l’histone, ce qui entraîne le relâchement de l’ADN et favorise la transcription. Les désacétylases sont des co-répresseurs qui éliminent les groupes acétyles, ce qui entraîne l’empaquetage serré de l’ADN autour des histones et empêche la transcription.
Par exemple, le co-régulateur SMRT s’associe au récepteur de l’hormone thyroïdienne au niveau de l’élément de réponse hormonale positive et agit comme un co-répresseur pour inhiber la transcription basale. Lorsqu’une hormone se lie au récepteur, le SMRT se dissocie et un co-activateur se lie pour activer la transcription. 
Cependant, lorsqu’il est lié au même récepteur sur un élément de réponse hormonale négatif, le SMRT active la transcription en l’absence de l’hormone. Agissant ainsi comme un co-activateur.

<ol>
	<li>Lee, J. W., Cheong, J., Lee, Y. C., Na, S. Y. et Lee, S. K. (2000). Dissection du mécanisme moléculaire de l’action des récepteurs nucléaires : coactivateurs de transcription et corépresseurs. Médecine expérimentale et moléculaire, 32(2), 53-60.</li>
	<li>Gao, Z., Chiao, P., Zhang, X., Zhang, X., Lazar, M. A., Seto, E., ... et Ye, J. (2005). Coactivateurs et corépresseurs de NF-κB dans le promoteur du gène IκBα. Journal de chimie biologique, 280(22), 21091-21098.</li>
	<li>Purcell, D. J., Jeong, K. W., Bittencourt, D., Gerke, D. S. et Stallcup, M. R. (2011). Un mécanisme distinct pour la fonction coactivateur par rapport à la fonction copresseur par l’histone méthyltransférase G9a dans la régulation transcriptionnelle. Journal de chimie biologique, 286(49), 41963-41971.</li>
</ol>

co-activateurs et co-répresseurs

Co-activators and Co-repressors

La transcription des gènes est régulée par l'action synergique de plusieurs protéines qui forment un complexe au niveau d'un site de régulation des gènes. Ceci est observé chez les eucaryotes, où la régulation de l’expression des gènes est un processus complexe. Les protéines régulatrices chez les eucaryotes peuvent globalement être classées en deux types : les régulateurs qui se lient directement à des séquences d'ADN spécifiques et les co-régulateurs qui s'associent aux protéines régulatrices mais ne peuvent pas se lier directement à l'ADN. Ces co-régulateurs sont ensuite divisés en co-activateurs ou co-répresseurs en fonction de leur fonction.

Un co-régulateur individuel peut fonctionner soit comme co-activateur, soit comme co-répresseur, selon son rôle dans son complexe associé. Par exemple, le co-répresseur transcriptionnel G9a participe à l'activation de l'expression génique d'un récepteur d'hormone stéroïde avec d'autres co-activateurs, tels que GRIP1 et CARM1. Des domaines distincts de la protéine remplissent ces fonctions variées. En plus de leur rôle dans le complexe, ces régulateurs ont des activités enzymatiques qui peuvent aider à réguler l'expression des gènes grâce au remodelage de la structure de la chromatine.

Les histones acétyltransférases et les histones déméthylases fonctionnent comme des co-activateurs ; cependant, ils doivent d’abord être localisés sur le site régulateur par un activateur de transcription pour pouvoir remplir ces fonctions. Les histones acétyltransférases peuvent acétyler les résidus de lysine sur les queues d'histone. L'acétylation déroule la chromatine et favorise l'expression des gènes. D'autre part, les histones désacétylases et les histones méthyltransférases fonctionnent comme des co-répresseurs. Ces deux modifications conduisent au resserrement de la structure de la chromatine et conduisent ainsi à la prévention de l’expression des gènes.

Co-activateurs et co-répresseurs

La transcription des gènes est régulée par l’action synergique de plusieurs protéines qui forment un complexe au niveau d’un site de régulation génique. C’est ce que l’on observe dans ...

Education

Enseignement

JoVE Core

Molecular Biology

Biologie moléculaire

Unit 1

Unité 1

Gene Expression

Expression génique

KEY TERMS AND CONCEPTS

TERMES ET CONCEPTS CLÉS

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 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.

Chromatin Control in Gene Transcription

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