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

대부분의 유전자의 발현은 하나 이상의 전사 인자에 의해 조절되며, 많은 유전자는 서로 다른 단백질 조합을 사용하여 켜거나 끕니다. 이 조합 유전자 조절은 진핵생물이 전사를 정확하게 조절할 수 있도록 합니다.
조합 유전자 조절은 유전자의 전사 여부와 전사 효율을 조절할 수 있습니다. 유전자 X의 전사에 영향을 미치는 세 가지 전사 인자 A, B, C를 고려하십시오. 
A가 없으면 유전자 X는 전사되지 않습니다. C가 없으면 유전자 X가 전사되지 않습니다. 그리고 B가 없으면 전사 효율이 감소합니다. 그러므로, 세 가지 조절인자의 조합은 유전자 X의 높은 수준의 전사를 위해 필요합니다.
전사 조절인자(transcriptional regulator)는 여러 유전자의 조절에 참여할 수 있습니다. A는 B 및 C와 함께 유전자 X의 전사를 일으키지만, A는 다른 전사 인자인 D와 함께 다른 유전자 Y의 전사를 자극할 수 있습니다. 이를 통해 몇 가지 전사 인자(transcription factor)가 많은 수의 유전자를 조절할 수 있습니다.
전사 인자는 서로 다른 계열로 분류되며 동일한 계열의 다른 단백질 또는 다른 계열의 단백질과 상승 작용적으로 기능할 수 있습니다.
POU 계열에 속하는 전사 인자는 집안일에서 세포 분화에 이르기까지 다양한 기능을 가진 유전자를 조절하지만, 이 계열에는 단백질이 거의 없으며 인간에는 15개에 불과합니다.
다양한 기능을 수행하는 능력은 다른 가족의 다른 전사 인자와의 조정에 달려 있습니다. 
조합 유전자 제어는 분화된 세포의 체외 재프로그래밍에 필요합니다. 체세포에서 전사 인자 Oct-4, Sox-2, Klf-4 및 c-Myc의 발현은 줄기세포로의 전환을 유발할 수 있습니다.
재프로그래밍은 처음 3개의 단백질 중 어느 것도 없는 경우 발생하지 않으며 c-Myc가 없으면 효율성이 낮은 재프로그래밍이 발생합니다. 네 가지 요인 모두의 조합 조절은 유도 만능 줄기 세포의 형성에 필요합니다.

<ol>
	<li>Reményi, A., Schöler, H. R., & Wilmanns, M. (2004). 유전자 발현의 조합 조절. 자연 구조 및 분자 생물학, 11(9), 812-815.</li>
	<li>Qi, H., & Pei, D. (2007). 4의 마법 : Oct4, Sox2, Myc 및 Klf4에 의한 체세포에서 만능 줄기 세포 유도.세포 연구, 17 (7), 578-580.</li>
	<li>Godini, R., & Fallahi, H. (2019). 초기 인간 배아 발달 중 전사 인자의 역학 변화. 세포 생리학 저널, 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). 전사 인자 및 결합 모티프의 조합 조절을 식별합니다. 게놈 생물학, 5(8), R56.</li>
</ol>

조합적 유전자 조절

Combinatorial Gene Control

조합적 유전자 조절은 단일 유전자의 발현을 조절하기 위한 여러 전사 인자의 시너지 작용입니다. 이러한 요인 중 하나 이상이 없으면 유전자 발현 또는 억제 수준에 상당한 차이가 발생할 수 있습니다.

30,000개 이상의 유전자 발현은 대략 2000~3000개의 전사 인자에 의해 제어됩니다. 이는 단일 전사 인자가 하나 이상의 조절 서열을 인식할 수 있기 때문에 가능합니다. 유전자 발현의 특이성은 다양한 유전자의 발현을 조절하기 위해 다양한 조합으로 서로 작용하는 이 단백질을 통해 발생합니다.

조합적 유전자 조절은 여러 가지 메커니즘을 통해 발생합니다. 효모에서는 세 가지 다른 메커니즘이 설명되었습니다. 대기 활성화 시스템에서는 유전자 발현을 조절하는 데 필요한 모든 전사 인자가 DNA에 결합하여 신호를 받을 때만 전사를 활성화합니다. 예를 들어, 세포 주기의 G1 단계 후반에 필요한 유전자를 조절하는 전사 인자는 G1 초기에 표적 유전자의 조절 부위에 결합합니다. 그러나 이는 사이클린-단백질 키나아제가 후기 G1 단계에서 활성화되는 경우에만 전사를 유도합니다.

결합기 조합 제어에서는 세포 주기의 특정 단계에 주로 필요한 전사 인자가 세포 주기 전체에 걸쳐 조절 서열에 부착된 상태로 유지되며 다른 단계 동안 유전자 조절에 협력적으로 참여합니다. 예를 들어, SBF와 Fkh2는 각각 G1 및 G2 단계에서 발현되어야 하는 유전자의 조절에 주로 관여하는 두 가지 전사 인자입니다. 그러나 S단계에서 발현되어야 하는 특정 필수 유전자도 SBF와 Fkh2의 결합 작용에 의해 조절됩니다.

공동 과정 조합은 다양한 세포 마디의 조절을 위해 다른 전사 인자의 다양한 조합에 의해 지원되는 단일 전사 인자의 사용을 포함합니다. 예를 들어, 세포 주기의 G1 단계에 필요한 유전자의 발현을 조절하는 전사 인자는 다른 조절 인자 세트와 결합하여 교배 과정에 필요한 유전자의 조절에도 참여합니다.

조합 유전자 조절(Combinatorial gene control)은 단일 유전자의 발현을 조절하기 위한 여러 전사 인자의 시너지 작용입니다. 하나가 없거나 ...

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 1

제1단원

Gene Expression

유전자 발현

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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 분자생물학은 명확하고 간결한 애니메이션을 통해 분자 단계에서 일어나는 세포 과정을 설명합니다.또한, 과학자가 직접 실험을 진행하는 실사 영상을 통해 분자생물학 개념의 응용 사례를 보여줍니다.

Gene Expression by Transcription Factor Combinations

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