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

Los activadores de transcripción son proteínas que se encargan de permitir que la ARN polimerasa inicie la transcripción. Tienen dos dominios esenciales: uno que se une al ADN y otro que activa la transcripción.
Los dominios de unión al ADN contienen uno de varios motivos estructurales característicos, incluidos motivos comunes como las estructuras de cremallera de hélice-giro-hélice, dedo de zinc y leucina. 
Un dominio hélice-giro-hélice está formado por dos hélices alfa unidas por una cadena de aminoácidos que representa el giro. Una hélice es responsable de reconocer la secuencia de ADN y encaja en el surco principal. Estas proteínas se unen al ADN como dímeros. 
Un dedo de zinc contiene una hélice alfa y una lámina beta de dos hebras unidas por un átomo de zinc. La hélice se une al surco principal con la ayuda de dos histidinas en su cadena de aminoácidos. 
Una cremallera de leucina está formada por dos monómeros que interactúan entre sí en forma de Y que se une al ADN. Los monómeros consisten en leucina en cada séptima posición en el extremo C-terminal que interactúa con la leucina en el monómero opuesto. El N-terminal del monómero, que está formado por motivos básicos, se une al ADN.
El otro dominio esencial en el activador, el dominio activador de la transcripción, recluta coactivadores, proteínas esenciales que median la unión de los activadores a la ARN polimerasa. Estos coactivadores promueven la transcripción a través de varios mecanismos, como la modificación de histonas, lo que resulta en un mayor acceso de la maquinaria transcripcional al ADN. 
Los activadores también pueden enviar señales a través de sus coactivadores para activar la ARN polimerasa e iniciar la transcripción.
En algunos casos, los activadores son esenciales para la elongación de la transcripción. Algunas polimerasas detienen la transcripción después de unos pocos nucleótidos y necesitan la presencia de un activador para reiniciar la transcripción. 
La transcripción de un solo gen puede ser regulada por varios activadores diferentes. Cuando más de un activador está involucrado en la regulación de la transcripción, pueden actuar sinérgicamente para aumentar drásticamente la tasa de transcripción en comparación con la de los activadores individuales.

<ol>
	<li>Ma, J. (2006). Activadores transcripcionales y mecanismos de activación. En Expresión y regulación génica (pp. 147-158). Springer, Nueva York, NY.</li>
	<li>Verde, M. R. (2005). Activación de la transcripción eucariota: justo en el blanco. Célula molecular, 18(4), 399-402.</li>
</ol>

activadores de la transcripción eucariotas

Eukaryotic Transcription Activators

Los activadores de la transcripción son proteínas que promueven la transcripción de genes de ADN a ARN. En la mayoría de los casos, estas proteínas contienen dos dominios separados: un dominio que se une al ADN y un dominio para activar la transcripción; sin embargo, en algunos casos, un solo dominio es responsable tanto de la unión como de la activación de la transcripción, como se observa en el receptor de glucocorticoides y MyoD.

Los dominios de unión son capaces de reconocer e interactuar con secuencias reguladoras del ADN. Estos dominios se clasifican en diferentes familias y se denominan según las características estructurales que permiten el reconocimiento y la unión del ADN. Algunos tipos comunes de dominios de unión incluyen motivos de cremallera de leucina, dedo de zinc y hélice-giro-hélice. Por el contrario, los dominios responsables de la activación de la transcripción genética suelen ser secuencias cortas y simples y menos complejas que los dominios de unión. Se clasifican según su composición de aminoácidos en categorías, como ricos en glutamina, ricos en prolina y ricos en alanina.

Los activadores de la transcripción ayudan en el reclutamiento de diversas proteínas necesarias para la transcripción, como factores de transcripción generales, ARN polimerasa y coactivadores. Todas estas proteínas juntas se conocen como complejo de preiniciación y dependen de activadores de la transcripción para su reclutamiento en la ubicación adecuada. Estos activadores pueden unirse a un sitio cercano al promotor del gen o a varios miles de pares de bases alejados del gen para llevar a cabo su función. En los casos en los que están unidos a un sitio alejado del gen, dependen de la flexibilidad del ADN para doblarlos y acercarlos al promotor del gen. Los activadores de la transcripción también son necesarios para continuar el alargamiento de la transcripción o el reinicio de la transcripción en los casos en que el proceso se detiene a mitad de camino. Se sabe que los activadores de la transcripción actúan de forma sinérgica. La transcripción lograda por la acción de múltiples activadores es mayor que la que ocurriría si se sumaran factores individuales trabajando por separado.

Al igual que otras proteínas, los activadores de la transcripción están sujetos a modificaciones postranscripcionales. En muchos casos, estas modificaciones ayudan a la regulación positiva de la transcripción. Por ejemplo, la acetilación de p53, un activador que regula los genes responsables de la supresión de tumores, aumenta su capacidad para unirse al ADN.

Activadores de la transcripción eucariotas

Los activadores de transcripción son proteínas que promueven la transcripción de genes de ADN a ARN. En la mayoría de los casos, estas proteínas contienen dos dominios separados ...

Education

Educación

JoVE Core

Molecular Biology

Biología Molecular

Unit 1

Unidad 1

Gene Expression

Expresión génica

KEY TERMS AND CONCEPTS

TÉRMINOS Y CONCEPTOS CLAVE

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 Biología Molecular presenta los procesos moleculares de la célula a través de lecciones claras y concisas de animaciones audiovisuales. Además, en los vídeos de científicos en acción, se muestran aplicaciones de estos conceptos mediante experimentos reales en laboratorios especializados.

How Transcription Activators Turn Genes On

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