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

Gli attivatori di trascrizione sono proteine responsabili di permettere all'RNA polimerasi di iniziare la trascrizione. Hanno due domini essenziali, uno che si lega al DNA e l'altro che attiva la trascrizione. I domini di legame del DNA contengono una tra diverse caratteristiche:motivi strutturali, compresi i motivi comuni, come l'elica-giro-elica, a dita di zinco, e le strutture a cerniera di leucine Un dominio elica-giro-elica, o helix-turn-helix, è composto da due alfa-eliche, unite insieme da una catena amminoacidica che rappresenta la curva.Un'elica è responsabile del riconoscimento della sequenza di DNA e si inserisce nel solco principale. Queste proteine si legano al DNA come dimeri. Un motivo a dita di zinco o zinc-finger, contiene un'alfa elica e un foglio beta a due filamenti, tenuti insieme da un atomo di zinco.L'elica si lega al solco maggiore con l'aiuto di due istidine e della sua catena aminoacidica. Una cerniera di leucina, o leucine-zip, è composta da due monomeri che interagiscono tra loro nella forma di una Y che si lega al DNA. I monomeri sono costituiti da leucina ad ogni settima posizione all'estremità C-terminale, che interagisce con la leucina sul monomero opposto.Il terminale N del monomero, che è costituito da motivi basici, si lega al DNA. Un altro dominio essenziale nell'attivatore, il dominio di attivazione della trascrizione, recluta coattivatori, ossia proteine essenziali che mediano il legame degli attivatori alla RNA polimerasi. Questi coattivatori, promuovono la trascrizione, attraverso diversi meccanismi, tra cui la modifica dell'istone, che porta ad un maggiore accesso del meccanismo trascrizionale al DNA.Gli attivatori possono anche inviare segnali tramite i loro coattivatori per attivare la RNA polimerasi e iniziare la trascrizione. In alcuni casi, gli attivatori sono essenziali per l'allungamento del trascritto. Alcune polimerasi interrompono la trascrizione dopo alcuni nucleotidi e necessitano della presenza di un attivatore per riprendere la trascrizione.La trascrizione di un singolo gene può essere regolata da diversi attivatori. Quando più di un attivatore è coinvolto, nella regolazione della trascrizione, possono agire sinergicamente per aumentare drasticamente la velocità di trascrizione rispetto a quella di attivatori individuali

<ol>
	<li>Ma, J. (2006). Attivatori trascrizionali e meccanismi di attivazione. In Espressione genica e regolazione (pp. 147-158). Springer, New York, NY.</li>
	<li>Verde, MR (2005). Attivazione della trascrizione eucariotica: proprio sul bersaglio. Cellula molecolare, 18(4), 399-402.</li>
</ol>

attivatori della trascrizione eucariotica

Eukaryotic Transcription Activators

Gli attivatori di trascrizione sono proteine che promuovono la trascrizione dei geni dal DNA all'RNA. Nella maggior parte dei casi, queste proteine contengono due domini separati: un dominio che si lega al DNA e un dominio per l'attivazione della trascrizione; tuttavia, in alcuni casi, un singolo dominio è responsabile sia del legame che dell'attivazione della trascrizione, come osservato nel recettore dei glucocorticoidi e nel MyoD.

I domini leganti sono in grado di riconoscere e interagire con sequenze regolatrici sul DNA. Questi domini sono classificati in diverse famiglie e denominati in base alle caratteristiche strutturali che consentono il riconoscimento e il legame del DNA. Alcuni tipi comuni di domini di legame includono i motivi della cerniera leucina, del dito di zinco e dei motivi elica-giro-elica. Al contrario, i domini responsabili dell’attivazione della trascrizione genica sono solitamente sequenze brevi e semplici e sono meno complessi dei domini leganti. Sono classificati in base alla composizione aminoacidica in categorie, come ricchi di glutammina, ricchi di prolina e ricchi di alanina.

Gli attivatori di trascrizione aiutano nel reclutamento di varie proteine necessarie per la trascrizione come fattori di trascrizione generali, RNA polimerasi e coattivatori. Tutte queste proteine insieme sono conosciute come il complesso di pre-inizio e dipendono da attivatori di trascrizione per il loro reclutamento nella posizione appropriata. Questi attivatori possono legarsi a un sito vicino al promotore del gene o a diverse migliaia di paia di basi di distanza dal gene per svolgere la loro funzione. Nei casi in cui sono legati a un sito lontano dal gene, si affidano alla flessibilità del DNA per piegarsi e portarli in prossimità del promotore del gene. Gli attivatori della trascrizione sono inoltre necessari per continuare l’allungamento di una trascrizione o per riavviare la trascrizione nei casi in cui il processo si interrompe a metà. È noto che gli attivatori della trascrizione agiscono in sinergia. La trascrizione ottenuta dall'azione di più attivatori è superiore a quella che avverrebbe come somma di singoli fattori che lavorano separatamente.

Come altre proteine, gli attivatori della trascrizione sono soggetti a modifiche post-trascrizionali. In molti casi queste modifiche aiutano nella regolazione positiva della trascrizione. Ad esempio, l’acetilazione di p53, un attivatore che regola i geni responsabili della soppressione del tumore, aumenta la sua capacità di legarsi al DNA.

Attivatori della trascrizione eucariotica

Gli attivatori della trascrizione sono proteine che promuovono la trascrizione di geni dal DNA all'RNA. Nella maggior parte dei casi, queste proteine contengono due domini separati ...

Education

Didattica

JoVE Core

Molecular Biology

Biologia Molecolare

Unit 1

Unità 1

Gene Expression

Espressione genica

KEY TERMS AND CONCEPTS

TERMINI E CONCETTI CHIAVE

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

Le video animazioni di JoVE Core Molecular Biology, organizzate in video lezioni, illustrano i processi molecolari cellulari in maniera chiara e concisa. Inoltre, nei video di "scienziati in azione", i concetti scientifici vengono applicati e dimostrati da ricercatori attraverso esperimenti in laboratorio.

How Transcription Activators Turn Genes On

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