Name: gene expression by transcription factor combinations
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 2 min 33 s
Channel: JoVE

Die Expression der meisten Gene wird durch mehr als einen Transkriptionsfaktor reguliert, wobei viele Gene mit unterschiedlichen Kombinationen von Proteinen ein- oder ausgeschaltet werden. Diese kombinatorische Genkontrolle ermöglicht es Eukaryoten, die Transkription präzise zu steuern.
Die kombinatorische Genkontrolle kann regulieren, ob ein Gen transkribiert wird, sowie seine transkriptionelle Effizienz. Betrachten Sie drei Transkriptionsfaktoren, A, B und C, die die Transkription eines Gens, X, beeinflussen. 
Wenn A fehlt, wird Gen X nicht transkribiert. Wenn C nicht vorhanden ist, wird Gen X nicht transkribiert. Und wenn B nicht vorhanden ist, nimmt die Transkriptionseffizienz ab. Daher ist die Kombination aller drei Regulatoren für ein hohes Maß an Transkription von Gen X notwendig.
Ein Transkriptionsregulator kann an der Regulation mehrerer Gene beteiligt sein. A zusammen mit B und C bewirken die Transkription von Gen X, aber A zusammen mit einem anderen Transkriptionsfaktor, D, kann die Transkription eines anderen Gens, Y, stimulieren. Dadurch können einige wenige Transkriptionsfaktoren eine große Anzahl von Genen regulieren.
Transkriptionsfaktoren werden in verschiedene Familien eingeteilt und können synergistisch wirken, entweder mit anderen Proteinen aus derselben Familie oder mit solchen aus verschiedenen Familien.
Transkriptionsfaktoren, die zur Familie der POU gehören, regulieren Gene mit einer Vielzahl von Funktionen, die von der Haushaltsführung bis zur Zelldifferenzierung reichen. Allerdings gibt es in dieser Familie nur sehr wenige Proteine, beim Menschen sind es nur fünfzehn.
Ihre Fähigkeit, ihre vielfältigen Funktionen zu erfüllen, hängt von ihrer Koordination mit anderen Transkriptionsfaktoren aus verschiedenen Familien ab. 
Die kombinatorische Genkontrolle ist für die in vitro Reprogrammierung differenzierter Zellen notwendig. Die Expression der Transkriptionsfaktoren Oct-4, Sox-2, Klf-4 und c-Myc in somatischen Zellen kann die Umwandlung in Stammzellen auslösen.
Die Reprogrammierung findet in Abwesenheit eines der ersten 3 Proteine nicht statt, und die Abwesenheit von c-Myc führt zu einer Reprogrammierung mit geringer Effizienz. Die kombinatorische Kontrolle aller vier Faktoren ist für die Bildung von induzierten pluripotenten Stammzellen notwendig.

<ol>
	<li>Reményi, A., Schöler, H. R., & Wilmanns, M. (2004). Kombinatorische Kontrolle der Genexpression. Natur Struktur- und Molekularbiologie, 11(9), 812-815.</li>
	<li>Qi, H., & Pei, D. (2007). Die Magie der Vier: Induktion von pluripotenten Stammzellen aus somatischen Zellen durch Oct4, Sox2, Myc und Klf4. Zellforschung, 17(7), 578-580.</li>
	<li>Godini, R., & Fallahi, H. (2019). Dynamische Veränderungen der Transkriptionsfaktoren während der frühen menschlichen Embryonalentwicklung. Zeitschrift für Zellphysiologie, 234(5), 6489–6502. https://doi.org/10.1002/jcp.27386</li>
	<li>Kato, M., Hata, N., Banerjee, N., Futcher, B., & Zhang, M. Q. (2004). Identifizierung der kombinatorischen Regulation von Transkriptionsfaktoren und Bindungsmotiven. Genombiologie, 5(8), R56.</li>
</ol>

kombinatorische genkontrolle

Combinatorial Gene Control

Kombinatorische Genkontrolle ist die synergetische Wirkung mehrerer Transkriptionsfaktoren, um die Expression eines einzelnen Gens zu regulieren. Das Fehlen eines oder mehrerer dieser Faktoren kann zu einem signifikanten Unterschied im Niveau der Genexpression oder -repression führen.

Die Expression von mehr als 30.000 Genen wird durch ungefähr 2000-3000 Transkriptionsfaktoren kontrolliert. Dies ist möglich, weil ein einzelner Transkriptionsfaktor mehr als eine regulatorische Sequenz erkennen kann. Die Spezifität in der Genexpression erfolgt durch das Zusammenwirken dieser Proteine in verschiedenen Kombinationen, um die Expression unterschiedlicher Gene zu regulieren.

Die kombinatorische Genkontrolle erfolgt durch mehrere unterschiedliche Mechanismen. In Hefen wurden drei verschiedene Mechanismen beschrieben. Im Warte-Aktivierungs-System binden alle Transkriptionsfaktoren, die benötigt werden, um die Expression eines Gens zu regulieren, an die DNA und aktivieren die Transkription erst, wenn sie ein Signal erhalten. Zum Beispiel binden Transkriptionsfaktoren, die Gene regulieren, die in der späten G1-Phase des Zellzyklus benötigt werden, in der frühen G1-Phase an die regulatorische Stelle ihrer Zielgene. Sie induzieren die Transkription jedoch erst, wenn eine Zyklin-Proteinkinase in der späten G1-Phase aktiviert wird.

Bei der gemeinsamen Phasen-kombinatorischen Kontrolle bleiben die hauptsächlich für eine bestimmte Phase des Zellzyklus erforderlichen Transkriptionsfaktoren während des gesamten Zellzyklus an die regulatorische Sequenz gebunden und beteiligen sich kooperativ an der Regulation von Genen während anderer Phasen. Zum Beispiel sind SBF und Fkh2 zwei Transkriptionsfaktoren, die hauptsächlich an der Regulation von Genen beteiligt sind, die in den G1- und G2-Phasen ausgedrückt werden müssen. Bestimmte essentielle Gene, die in der S-Phase ausgedrückt werden müssen, werden jedoch auch durch das kombinierte Wirken von SBF und Fkh2 reguliert.

Die gemeinsame Prozesskombination beinhaltet die Verwendung eines einzelnen Transkriptionsfaktors, der durch unterschiedliche Kombinationen anderer Transkriptionsfaktoren bei der Regulation verschiedener zellulärer Prozesse unterstützt wird. Zum Beispiel beteiligen sich Transkriptionsfaktoren, die die Expression von Genen in der G1-Phase des Zellzyklus regulieren, auch an der Regulation von Genen, die für den Paarungsprozess erforderlich sind, in Verbindung mit einem anderen Satz von Regulatoren.

Kombinatorische Genkontrolle

Kombinatorische Genkontrolle ist die synergistische Wirkung mehrerer transkriptioneller Faktoren, um die Expression eines einzelnen Gens zu regulieren. Das Fehlen eines oder ...

Education

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JoVE Core

Molecular Biology

Molekularbiologie

Unit 1

Einheit 1

Gene Expression

Genexpression

KEY TERMS AND CONCEPTS

KERNBEGRIFFE UND KONZEPTE

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 3,000 transcription factors. A single transcription factor can recognize more than one regulatory sequence. Because of this, different proteins can team up in many ways to give each gene its own expression pattern.

In yeast, one form is the waiting-activating system. Here, the transcription factors needed for a gene bind to DNA first, but they do not turn on transcription right away. They activate the gene only after they receive a signal. For example, factors that regulate genes needed in late G1 bind their target sites in early G1 and activate transcription only when a cyclin-protein kinase becomes active in late G1.

Another form is joint-phase combinatorial control. In this system, transcription factors that mainly work in one cell-cycle phase stay attached to the regulatory sequence throughout the cell cycle. They also help regulate genes during other phases. SBF and Fkh2 are examples. They mainly regulate genes in G1 and G2, but they also work together to control certain essential S-phase genes.

A third form is the joint-process combination. In this case, one transcription factor works with different sets of partners to control different cellular processes. For example, transcription factors that regulate genes needed in G1 also take part in regulating mating genes when they join with a different group of regulators. This shows how the same protein can support more than one gene program depending on its partners.

Gene Expression by Transcription Factor Combinations

gene-expression-by-transcription-factor-combinations

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

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 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 factors work in combinations to control gene expression, including yeast examples like waiting-activating, joint-phase, and joint-process control.

Gene Expression by Transcription Factor Combinations | JoVE K12

molecular biology

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Gene Expression by Transcription Factor Combinations

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