Name: how transcription factors bind dna
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 2 min 13 s
Channel: JoVE

Los reguladores transcripcionales son proteínas que reconocen y se unen a secuencias cortas de ADN conocidas como secuencias cis-reguladoras. Debido a que estas secuencias suelen tener menos de diez nucleótidos, las posibilidades de que la misma secuencia ocurra aleatoriamente en el genoma son muy altas.
Muchos reguladores forman un par de dímeros para limitar la unión a secuencias aleatorias. Un dímero puede unirse a secuencias de más de diez nucleótidos, lo que hace menos probable que la secuencia esté presente aleatoriamente en el genoma y aumenta la especificidad de unión.
Estos dímeros reguladores pueden ser un homodímero hecho de los mismos tipos de monómero o un heterodímero con diferentes tipos de monómeros. Debido a que los pares pueden estar compuestos por diferentes monómeros, las diversas combinaciones permiten unirse a diferentes secuencias sin necesidad de nuevos tipos de proteínas.
Cuando no están unidos al ADN, los reguladores cooperativos existen como monómeros que a veces forman dímeros a través de interacciones débiles y no covalentes; sin embargo, estas estructuras forman dímeros estrechamente asociados cuando se unen al ADN debido a la unión cooperativa.
La unión cooperativa es un fenómeno en el que la unión de un monómero a la secuencia cis-reguladora aumenta la probabilidad de una segunda unión del regulador debido a cambios estructurales. Esto permite que un segundo regulador se una firmemente al otro lado del sitio de unión y forme un dímero con el primero.
Esto significa que la mayoría de las veces, todas las instancias de secuencias cis-reguladoras específicas tienen un regulador unido o ninguna de ellas lo tiene. 
Para muchos genes, el ADN se envuelve firmemente alrededor de las proteínas histonas, lo que impide que los reguladores transcripcionales accedan a las secuencias cis-reguladoras. Sin embargo, el extremo del ADN suelto permite cierto espacio para la unión. La unión de un solo regulador en este sitio puede ayudar a desenrollar la estructura, permitiendo así que los otros reguladores se unan.

<ol>
	<li>Alberts et al., 6ª edición; páginas 375, 378-380</li>
	<li>Morgunova, E., & Taipale, J. (2017). Perspectiva estructural de la unión cooperativa de factores de transcripción. Opinión actual en biología estructural, 47, 1-8.</li>
</ol>

unión cooperativa de reguladores de transcripción

Cooperative Binding of Transcription Regulators

Los reguladores transcripcionales se unen a secuencias reguladoras cis específicas en el ADN para regular la transcripción genética. Estas secuencias reguladoras en cis son muy cortas, generalmente de menos de diez pares de nucleótidos de longitud. La corta longitud significa que existe una alta probabilidad de que exactamente la misma secuencia ocurra aleatoriamente en todo el genoma. Dado que los reguladores también pueden unirse a grupos de secuencias similares, esto aumenta aún más las posibilidades de unión aleatoria. Los reguladores transcripcionales forman dímeros que se unen a una secuencia el doble de tiempo que un monómero, lo que aumenta las secuencias y reduce las posibilidades de unión aleatoria. Los dímeros reguladores de la transcripción pueden ser homodímeros o heterodímeros. En solución, estos reguladores cooperativos existen como monómeros o dímeros débilmente unidos. Sin embargo, cuando estos monómeros se unen a una secuencia reguladora cis extendida en el ADN, forman dímeros estables.

La cooperatividad es un fenómeno en el que la unión de una proteína monomérica provoca cambios estructurales en el ADN y aumenta la afinidad de los sitios reguladores por otros monómeros. Esto permite que los monómeros se unan como dímeros en la secuencia reguladora cis. Este fenómeno también ayuda a los reguladores a acceder a sitios ubicados en el ADN que están estrechamente unidos a las proteínas histonas en el nucleosoma, que de otro modo serían inaccesibles. La primera unión suele ocurrir en el ADN al final del nucleosoma, donde no está estrechamente unido. La unión en este sitio hace que el ADN se aleje de las histonas, lo que provoca el descompacto del nucleosoma. Este desembalaje aumenta el acceso a los otros sitios regulatorios. En eucariotas, la unión del factor de transcripción depende predominantemente de la cooperatividad. Aunque en algunos casos puede ocurrir cooperatividad, la mayor parte de la unión de los reguladores transcripcionales en procariotas no es cooperativa. En tales casos, los reguladores existen como dímeros estables unidos por varias interacciones no covalentes.

Se puede determinar si un regulador desconocido se une de forma cooperativa o no cooperativa trazando el número de sitios de unión ocupados en el ADN frente a la concentración de proteína. Si la gráfica es una curva en forma de S, indica que el regulador se une cooperativamente a los sitios de unión. Si la curva aumenta de manera constante antes de estabilizarse a medida que se acerca a todos los sitios de unión ocupados, indica que la unión no es cooperativa.

Unión cooperativa de reguladores de transcripción

Los reguladores transcripcionales se unen a secuencias cis-reguladoras específicas en el ADN para regular la transcripción de genes. Estas secuencias cis-reguladoras son ...

cooperative-binding-of-transcription-regulators

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 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 sequence that is twice as long as the sequence bound by a monomer. These dimers can be homodimers or heterodimers.

In solution, cooperative regulators may exist as monomers or as weakly linked dimers. When they bind to an extended cis-regulatory sequence on DNA, they form stable dimers. Cooperativity means that the binding of one monomer changes the DNA structure and increases the site’s affinity for other monomers. This helps the proteins bind together as dimers on the cis-regulatory sequence.

Cooperativity also helps regulators reach sites on DNA that are tightly wrapped around histone proteins in the nucleosome. These sites are usually hard to access. Binding often starts at the end of the nucleosome, where the DNA is less tightly packed. That first binding step can pull the DNA away from the histones and help unpack the nucleosome, which makes other regulatory sites easier to reach.

In eukaryotes, transcription factor binding depends mainly on cooperativity. In prokaryotes, most transcriptional regulator binding is non-cooperative, although cooperativity can occur in some cases. Non-cooperative regulators are usually stable dimers held together by several non-covalent interactions. The difference can be seen by plotting occupied binding sites against protein concentration. An S-shaped curve suggests cooperative binding, while a steady rise that levels off suggests non-cooperative binding.

How Transcription Factors Bind DNA

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

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

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 transcription regulators bind cis-regulatory DNA, form dimers, unpack nucleosomes, and how S-shaped curves reveal cooperative binding.

How Transcription Factors Bind DNA | 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 Factors Bind DNA

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