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

Çoğu genin ekspresyonu birden fazla transkripsiyon faktörü tarafından regüle edilir ve farklı protein kombinasyonları kullanılarak birçok gen açılır ve kapatılır. Bu kombinatoryal gen kontrolü, ökaryotların transkripsiyonu tam olarak kontrol etmelerine olanak sağlar. Kombinatoryal gen kontrolü, bir genin transkribe edilip edilmeyeceğini ve transkripsiyon verimliliğini regüle eder.X geninin transkripsiyonunu etkileyen A, B ve C olmak üzere üç transkripsiyon faktörü olduğunu düşünelim. A yoksa, X geni transkribe edilmeyecektir. C yoksa, X geni transkribe edilmeyecektir.B yoksa, transkripsiyon verimliliği düşecektir. Bu nedenle, X geninin yüksek düzeyde transkripsiyonu için her üç regülatörün kombinasyonu gereklidir. Bir transkripsiyon regülatörü birçok genin regülasyonunda rol alabilir.B ve C ile birlikte A, X geninin transkripsiyonuna neden olur;ancak A, başka bir transkripsiyon faktörü olan D ile birlikte, farklı bir gen olan Y'nin transkripsiyonunu tetikleyebilir. Bu, birkaç transkripsiyon faktörünün çok sayıda geni regüle etmesine izin verir. Transkripsiyon faktörleri farklı ailelere ayrılır ve aynı aileden diğer proteinlerle veya farklı ailelerden proteinlerle sinerji içerisinde işlev görebilir.Pou ailesine ait transkripsiyon faktörleri, housekeeping'den hücre farklılaşmasına kadar çeşitli işlevlere sahip genleri regüle eder. Bununla birlikte, bu ailede çok az sayıda protein vardır;insanlarda bu sayı sadece 15'tir. Farklı işlevlerini yerine getirme kabiliyetleri, farklı ailelerden diğer transkripsiyon faktörleriyle koordinasyonlarına bağlıdır.Kombinatoryal gen kontrolü, farklılaşmış hücrelerin in vitro olarak yeniden programlanması için gereklidir. Somatik hücrelerde, Eki-4, Sox-2, Klf-4 ve c-Myc transkripsiyon faktörlerinin ekspresyonu, kök hücrelere dönüşümü tetikleyebilir. İlk üç proteinden herhangi birinin yokluğunda, yeniden programlama gerçekleşmez.Ve c-Myc'nin yokluğu, düşük verimlilikte yeniden programlamaya neden olur. Uyarılmış pluripotent kök hücrelerin oluşumu için dört faktörün tümünün kombinatoryal kontrolü gereklidir.

<ol>
	<li>Reményi, A., Schöler, H. R., & Wilmanns, M. (2004). Gen ekspresyonunun kombinatoryal kontrolü. Doğa yapısal ve moleküler biyoloji, 11(9), 812-815.</li>
	<li>Qi, H. ve Pei, D. (2007). Dördün büyüsü: Oct4, Sox2, Myc ve Klf4 ile somatik hücrelerden pluripotent kök hücrelerin indüksiyonu. Hücre araştırması, 17(7), 578-580.</li>
	<li>Godini, R. ve Fallahi, H. (2019). Erken insan embriyonik gelişimi sırasında transkripsiyon faktörlerindeki dinamik değişiklikler. Hücresel fizyoloji dergisi, 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). Transkripsiyon faktörlerinin ve bağlanma motiflerinin kombinatoryal regülasyonunun belirlenmesi. Genom biyolojisi, 5(8), R56.</li>
</ol>

kombinasyonal gen kontrolü

Combinatorial Gene Control

Kombinasyonal gen kontrolü, tek bir genin ifadesini düzenlemek için çeşitli transkripsiyonel faktörlerin sinerjistik etkisidir. Bu faktörlerden bir veya daha fazlasının yokluğu, gen ifadesi veya baskısı düzeyinde önemli bir farklılığa yol açabilir. 30.000'den fazla genin ifadesi yaklaşık 2000-3000 transkripsiyon faktörü tarafından kontrol edilmektedir. Bu mümkündür çünkü tek bir transkripsiyon faktörü birden fazla düzenleyici diziyi tanıyabilir. Gen ifadesindeki spesifiklik, bu proteinlerin farklı genlerin ifadesini düzenlemek için çeşitli kombinasyonlarda birbirleriyle çalışmasıyla ortaya çıkar. Kombinasyonal gen kontrolü birkaç farklı mekanizma yoluyla gerçekleşir. Mayada üç farklı mekanizma tanımlanmıştır. Bekletici-aktive edici sistemde, bir genin ifadesini düzenlemek için gereken tüm transkripsiyon faktörleri DNA'ya bağlanır ve yalnızca bir sinyal aldıklarında transkripsiyonu etkinleştirir. Örneğin, hücre döngüsünün geç G1 fazında ihtiyaç duyulan genleri düzenleyen transkripsiyon faktörleri, erken G1'de hedef genlerinin düzenleyici bölgesine bağlanır. Bununla birlikte, yalnızca geç G1 fazında bir siklin-protein kinaz aktive edildiğinde transkripsiyonu indüklerler. Eklem fazlı kombinasyonal kontrolde, öncelikle hücre döngüsünün belirli bir fazı için gerekli olan transkripsiyon faktörleri, hücre döngüsü boyunca düzenleyici diziye bağlı kalır ve diğer fazlar sırasında genlerin düzenlenmesine kooperatif bir şekilde katılır. Örneğin SBF ve Fkh2, sırasıyla G1 ve G2 fazlarında ifade edilmesi gereken genlerin düzenlenmesinde öncelikli olarak yer alan iki transkripsiyon faktörüdür. Bununla birlikte, S-fazında ifade edilmesi gereken bazı temel genler de SBF ve Fkh2'nin birleşik etkisi ile düzenlenir. Ortak proses kombinasyonu, farklı hücresel proseslerin düzenlenmesi için diğer transkripsiyon faktörlerinin farklı kombinasyonları tarafından desteklenen tek bir transkripsiyon faktörünün kullanımını içerir. Örneğin, hücre döngüsünün G1 fazında ihtiyaç duyulan genlerin ifadesini düzenleyen transkripsiyon faktörleri, aynı zamanda farklı düzenleyicilerle birlikte çiftleşme süreci için gerekli genlerin düzenlenmesine de katılır.

Kombinasyonal Gen Kontrolü

Kombinatoryal gen kontrolü, tek bir genin ekspresyonunu düzenlemek için çeşitli transkripsiyonel faktörlerin sinerjik etkisidir. Birinin olmaması veya ...

Education

JoVE Core

Molecular Biology

Moleküler Biyoloji

Unit 1

Ünite 1

Gene Expression

Gen İfadesi

KEY TERMS AND CONCEPTS

TEMEL TERİMLER VE KAVRAMLAR

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

JoVE Core Moleküler Biyoloji, hücrenin moleküler süreçlerini açık ve özlü animasyonlu video dersleriyle sergiler. Buna ek olarak, bilim insanı-eylem videolarında, bu kavramların uygulaması modern laboratuvarlarda gerçek deneylerle gösterilmektedir.

Gene Expression by Transcription Factor Combinations

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