Name: how cells switch genes on and off
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 1 min 58 s
Channel: JoVE

다세포 유기체의 몸에 있는 모든 세포는 동일한 DNA를 가지고 있습니다. 그러나 다른 세포 유형은 세포 내 유전자의 차등 발현에 기인할 수 있는 현저한 구조적 및 기능적 차이를 가지고 있습니다. 
또한 특정 세포는 세포 또는 유기체의 변화로 인해 시간이 지남에 따라 다른 유전자를 발현합니다. 생산되는 RNA와 단백질의 다양성은 세포가 적절한 시기에 고유한 기능을 수행할 수 있도록 합니다.
간세포라고 하는 간 세포는 뉴런과 다른 유전자 세트를 발현합니다.
예를 들어, 간 세포는 독성 알코올을 아세트알데히드로 분해하는 효소인 알코올 탈수소효소를 생산한 다음 추가로 대사되어 이산화탄소와 물을 생산할 수 있습니다. 
대조적으로, 뉴런은 한 뉴런에서 인접한 뉴런으로 정보를 전달하는 데 도움이 되는 뇌의 단백질 그룹인 뉴렉신을 생성합니다. 
세포는 전사 및 번역 전, 도중 및 후에 여러 조절 단계에서 유전자 발현을 제어하는 메커니즘을 가지고 있습니다. 그러나 전사 조절인자(transcriptional regulator)는 mRNA 전사체의 합성을 막기 때문에 일반적입니다. 
인간의 간 발달 과정에서 전사 인자 C/EBP α, C/EBP β 및 Hepatocyte Nuclear Factor-1은 알코올 탈수소효소 유전자의 간 특이적 발현에 기여합니다. 
유전자 발현은 또한 세포 외 환경에 대한 반응으로 조절됩니다. 
혈당 수치가 감소하면 췌장에서 글루카곤 호르몬을 분비합니다. 글루카곤에 노출되면 간세포는 비탄수화물 전구체에서 포도당 생산에 필요한 단백질인 포스포에놀피루베이트 카르복시키나아제를 발현합니다.

<ol>
	<li>Alberts et al., 6판; 369-374페이지.</li>
	<li>Lodish et al., 8판; 363-364페이지</li>
	<li>Park, Edwards A. Austin L. Gurney, Steven E. Nizielski, Parvin Hakimi, Zhodan Caot, Antoon MoormanY 및 Richard W. Hanson."포스포에놀피루베이트 카르복시키나제(GTP)에 대한 유전자의 전사 제어에서 CCAAT/Enhancer-binding Protein β 및 cAMP Regulatory Element-binding Protein의 상대적 역할" Journal of Biological Chemistry 268, No. 1, (1993): 613-619</li>
</ol>

세포 특이적 유전자 발현

Cell Specific Gene Expression

다세포 유기체는 구조적으로나 기능적으로 서로 다른 다양한 세포 유형을 포함하지만 모든 세포의 DNA는 동일한 모세포에서 유래합니다. 세포의 차이는 차등적인 유전자 발현에 기인할 수 있습니다. 혈액 해독, 지방 대사를 위한 담즙 생성, 대사에 필수적인 단백질 합성 등의 기능을 수행하는 간세포는 기능을 수행하기 위해 특정 유전자 세트를 발현해야 합니다. 유전자 발현은 발달 단계에 따라 달라집니다. 간세포로 분화되기 전에 세포는 세포주기, DNA 복제 및 증식에 관여하는 유전자를 발현합니다. 발달 후반에는 상피 분화와 혈액 응고에 관여하는 유전자가 많이 발현됩니다. 세포가 간세포로 분화되면 지질 대사 및 콜레스테롤 조절과 관련된 간 관련 기능과 관련된 유전자의 발현이 증가합니다.

유전자 발현은 전사, 번역, RNA 처리 및 수송, 번역 후 변형을 비롯한 여러 지점에서 조절될 수 있습니다. 발현을 조절하는 일반적인 방법은 특정 유전자의 전사를 조절하기 위해 DNA에 직접 결합하는 요소입니다. 간에서의 유전자 발현은 특히 전사 인자 C/EBPα, C/EBPβ 및 간세포 핵 인자-1에 의해 조절될 수 있습니다. 염색질에 포함된 히스톤을 변경하여 전사 전에 조절이 발생할 수 있습니다. 이러한 변형으로 인해 DNA 구조가 느슨해지거나 조여져 전사 조절자가 DNA에 접근하는 것을 각각 방지하거나 허용하게 됩니다. 세포 유형에 따라 공유 결합 변형과 히스톤 변형이 다르므로 유전자 접근성이 달라집니다.

세포는 환경 변화를 겪으며 이러한 세포외 자극에 반응하여 다양한 유전자를 발현합니다. 포도당은 중요한 에너지원이며 혈류 내 농도가 변동함에 따라 유기체는 유전자 및 단백질 발현의 적절한 변화에 반응해야 합니다. 혈당 수치가 감소하면 췌장에서는 글루카곤이라는 호르몬이 분비됩니다. 이 호르몬은 간에 신호를 보내 비탄수화물 전구체로부터 포도당을 생산하는 데 필요한 단백질인 포스포엔올피루브산 카복시키네이스(PEPCK)의 생성을 시작합니다. 글루카곤은 전사 인자 C/EBPα 및 C/EBPβ가 PEPCK 프로모터에 결합하도록 간접적으로 자극하여 이 유전자의 전사를 유도합니다. 혈당 수치가 높으면 췌장은 인슐린 호르몬을 분비합니다. PEPCK 유전자에는 전사를 억제하는 인슐린 반응 서열이 있습니다.

다세포 유기체는 구조적으로나 기능적으로 구별되는 다양한 세포 유형을 포함하지만 모든 세포의 DNA는 동일한 세포에서 유래했습니다.

Education

교육

JoVE Core

Molecular Biology

분자생물학

Unit 1

제1단원

Gene Expression

유전자 발현

KEY TERMS AND CONCEPTS

주요 용어 및 개념

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. Gene expression also changes during development. Before cells differentiate into liver cells, they express genes for the cell cycle, DNA replication, and cell growth. Later, genes for epithelial differentiation and blood coagulation become highly active. After the cells become hepatocytes, genes linked to liver functions, such as lipid metabolism and cholesterol control, increase in expression.

Cells can regulate gene expression at several steps, including transcription, translation, RNA processing and transport, and post-translational modifications. One common control point is transcription, where proteins bind DNA and affect whether a gene is copied into RNA. In the liver, transcription factors such as C/EBPα, C/EBPβ, and Hepatocyte Nuclear Factor-1 help regulate gene activity.

Control can also happen before transcription begins. Histones are proteins around which DNA is wrapped in chromatin. Chemical changes to histones can loosen or tighten the DNA structure. Looser chromatin gives transcription regulators access to the DNA, while tighter chromatin can block access. Different cell types have different covalent modifications and histone variants, which changes which genes are available to be expressed.

Environmental signals can also change gene expression. Blood glucose levels are one example. When glucose levels drop, the pancreas releases glucagon. This hormone signals the liver to make phosphoenolpyruvate carboxykinase, or PEPCK, a protein needed to produce glucose from non-carbohydrate sources. Glucagon increases transcription of the PEPCK gene by indirectly helping C/EBPα and C/EBPβ bind to its promoter. When blood glucose is high, the pancreas releases insulin, and an insulin-responsive sequence inhibits PEPCK transcription.

How Cells Switch Genes On and Off

cell specific gene expression

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 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 cells control gene expression through development, chromatin changes, transcription factors, and hormone signals like glucagon and insulin.

How Cells Switch Genes On and Off | 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.

How Cells Switch Genes On and Off

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