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

Die Transkription wird durch Aktivatoren und Repressoren reguliert, Proteine, die an die DNA binden. In Eukaryoten benötigen diese regulatorischen Proteine oft zusätzliche Proteine, sogenannte Co-Regulatoren, um richtig zu funktionieren.
Diese Co-Regulatoren binden an Aktivator- oder Repressorkomplexe, erkennen jedoch keine cis-regulatorischen Sequenzen, da sie nicht direkt an die DNA binden können. 
Ein transkriptioneller Regulator bindet an eine cis-regulatorische Sequenz, bevor der Co-Regulator assoziiert; Regulatoren und Co-Regulatoren können oft keine stabilen Komplexe bilden, es sei denn, der Regulator ist an die DNA gebunden. In bestimmten Fällen dienen RNA-Moleküle auch als Gerüste, um alle Proteine in einem Komplex zusammenzuhalten.
Einige dieser Co-Regulatoren sind Enzyme, die die Genexpression regulieren können, wie z. B. Histon-Acetyltransferasen und Deacetylasen.
Acetyltransferasen sind Co-Aktivatoren, die eine Acetylgruppe auf das Histon übertragen, was zur Auflockerung der DNA und zur Förderung der Transkription führt. Deacetylasen sind Co-Repressoren, die Acetylgruppen entfernen, was zu einer dichten Packung der DNA um die Histone führt und die Transkription verhindert.
Zum Beispiel assoziiert der Co-Regulator SMRT mit dem Schilddrüsenhormonrezeptor am positiven Hormonreaktionselement und wirkt als Co-Repressor, um die basale Transkription zu hemmen. Wenn ein Hormon an den Rezeptor bindet, dissoziiert die SMRT und ein Co-Aktivator bindet an die Aktivierung der Transkription. 
Wenn SMRT jedoch an denselben Rezeptor auf einem negativen Hormonreaktionselement gebunden ist, aktiviert es die Transkription in Abwesenheit des Hormons. Dadurch fungiert er als Co-Aktivator.

<ol>
	<li>Lee, J. W., Cheong, J., Lee, Y. C., Na, S. Y., & Lee, S. K. (2000). Entschlüsselung des molekularen Mechanismus der Kernrezeptorwirkung: Transkriptionskoaktivatoren und Corepressoren. Experimentelle und molekulare Medizin, 32(2), 53-60.</li>
	<li>Gao, Z., Chiao, P., Zhang, X., Zhang, X., Lazar, M. A., Seto, E., ... & Ye, J. (2005). Koaktivatoren und Corepressoren von NF-κB im IκBα-Genpromotor. Zeitschrift für Biologische Chemie, 280(22), 21091-21098.</li>
	<li>Purcell, D. J., Jeong, K. W., Bittencourt, D., Gerke, D. S., & Stallcup, M. R. (2011). Ein eindeutiger Mechanismus für die Funktion von Koaktivator und Corepressor durch die Histon-Methyltransferase G9a bei der transkriptionellen Regulation. Zeitschrift für Biologische Chemie, 286(49), 41963-41971.</li>
</ol>

koaktivatoren und korepressoren

Co-activators and Co-repressors

Die Gen-Transkription wird durch die synergetische Wirkung mehrerer Proteine reguliert, die an einer genregulatorischen Stelle einen Komplex bilden. Dies wird bei Eukaryoten beobachtet, wo die Regulation der Genexpression ein komplexer Prozess ist. Regulatorische Proteine bei Eukaryoten können grob in zwei Typen eingeteilt werden – Regulatoren, die direkt an spezifische DNA-Sequenzen binden, und Koregulatoren, die sich mit regulatorischen Proteinen assoziieren, aber nicht direkt an die DNA binden können. Diese Koregulatoren werden weiter in Koaktivatoren oder Korepressoren unterteilt, basierend auf ihrer Funktion.

Ein einzelner Koregulator kann entweder als Koaktivator oder als Korepressor fungieren, abhängig von seiner Rolle im zugehörigen Komplex. Zum Beispiel beteiligt sich der transkriptionelle Korepressor G9a an der Aktivierung der Genexpression für einen Steroidhormonrezeptor zusammen mit anderen Koaktivatoren wie GRIP1 und CARM1. Unterschiedliche Domänen des Proteins führen diese verschiedenen Funktionen aus. Zusätzlich zu ihrer Rolle im Komplex haben diese Regulatoren enzymatische Aktivitäten, die durch das Umgestalten der Chromatinstruktur bei der Regulierung der Genexpression helfen können.

Histone-Acetyltransferasen und Histone-Demethylasen funktionieren als Koaktivatoren; sie müssen jedoch zunächst von einem Transkriptionsaktivator an die regulatorische Stelle lokalisiert werden, um diese Funktionen ausführen zu können. Histone-Acetyltransferasen können die Lysinreste an den Histonschwänzen acetylieren. Die Acetylierung entrollt das Chromatin und fördert die Genexpression. Andererseits fungieren Histone-Deacetylasen und Histone-Methyltransferasen als Korepressoren. Beide Modifikationen führen zu einer Verdichtung der Chromatinstruktur und verhindern dadurch die Genexpression.

Koaktivatoren und Korepressoren

Die Gentranskription wird durch die synergistische Wirkung mehrerer Proteine reguliert, die an einer genregulatorischen Stelle einen Komplex bilden. Dies ist bei ...

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Lehre

JoVE Core

Molecular Biology

Molekularbiologie

Unit 1

Einheit 1

Gene Expression

Genexpression

KEY TERMS AND CONCEPTS

KERNBEGRIFFE UND KONZEPTE

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

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Chromatin Control in Gene Transcription

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