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

多細胞生物の体内のすべての細胞は同じDNAを持っています。しかし、異なる細胞タイプは顕著な構造的および機能的な違いを持っており、それは細胞内の遺伝子の発現の違いに起因する可能性があります。 
さらに、特定の細胞は、細胞や生物の変化により、時間の経過とともに異なる遺伝子を発現します。生成されるRNAとタンパク質の多様性により、細胞は適切なタイミングで独自の機能を実行することができます。
肝細胞と呼ばれる肝臓細胞は、ニューロンとは異なる遺伝子セットを発現します。
例えば、肝細胞はアルコールデヒドロゲナーゼという有毒なアルコールをアセトアルデヒドに分解する酵素を生成し、さらにそれを代謝して二酸化炭素と水を生成します。 
対照的に、ニューロンは脳内のタンパク質群であるニューレキシンを産生し、1つのニューロンから隣接するニューロンに情報を伝達するのを助けます。 
細胞は、転写と翻訳の前、最中、後の複数の調節ステップで遺伝子発現を制御するメカニズムを持っています。しかし、転写調節因子はmRNA転写産物の合成を妨げるため、一般的です。 
ヒトの肝臓の発達中、転写因子C/EBP α、C/EBP β、および肝細胞核因子-1がアルコールデヒドロゲナーゼ遺伝子の肝臓特異的発現に寄与します。 
遺伝子発現も細胞外環境に応答して調節されています。 
血糖値が下がると、膵臓はホルモンのグルカゴンを分泌します。グルカゴンにさらされると、肝細胞は非炭水化物前駆体からのグルコースの生成に必要なタンパク質であるホスホエノールピルビン酸カルボキシキナーゼを発現します。

<ol>
	<li>Alberts et al., 6th edition; pages 369-374.</li>
	<li>Lodish et al., 8th edition; pages 363-364 (英語</li>)
	<li>Park, Edwards A. Austin L. Gurney, Steven E. Nizielski, Parvin Hakimi, Zhodan Caot, Antoon MoormanY, and Richard W. Hanson. "Relative Roles of CCAAT/Enhancer-binding Protein β and cAMP Regulatory Element-binding Protein in Controlling Transcription of the Gene for Phosphoenolpyruvate Carboxykinase (GTP)" Journal of Biological Chemistry 268, No. 1, (1993): 613-619</li>
</ol>

細胞特異的遺伝子発現

Cell Specific Gene Expression

多細胞生物には、構造的および機能的に異なるさまざまな種類の細胞が含まれていますが、すべての細胞内のDNAは同じ親細胞に由来します。細胞の違いは、遺伝子発現の違いに起因すると考えられます。肝細胞の機能には、血液の解毒、脂肪を代謝するための胆汁の生成、代謝に必須のタンパク質の合成が含まれますが、その機能を実行するには特定の遺伝子セットを発現する必要があります。 遺伝子発現も発達段階によって異なります。肝細胞に分化する前に、細胞は細胞周期、DNA複製、および増殖に関与する遺伝子を発現します。発生の後半では、上皮分化と血液凝固に関与する遺伝子が高度に発現されます。細胞が肝細胞に分化すると、脂質代謝やコレステロール調節に関与する遺伝子など、肝臓特有の機能に関与する遺伝子の発現が増加します。

遺伝子発現は、転写、翻訳、RNAのプロセシングと輸送、翻訳後修飾などの多くの点で制御されます。発現を調節する一般的な方法は、DNAに直接結合して特定の遺伝子の転写を調節する因子です。肝臓における遺伝子発現は、転写因子C/EBPα、C/EBPβ、肝細胞核因子-1などによって制御されます。 調節は、クロマチンに含まれるヒストンを変化させることによって、転写の前に起こる可能性があります。これらの修飾はDNA構造の緩みまたは引き締めをもたらし、それによってそれぞれ転写調節因子のDNAへのアクセスを防止または許可します。 細胞の種類が異なれば、共有結合修飾やヒストン変異体も異なるため、遺伝子へのアクセス可能性が異なります。

細胞は環境変化にさらされ、これらの細胞外刺激に応答してさまざまな遺伝子を発現します。グルコースは重要なエネルギー源であり、血流中のグルコース濃度が変動するため、生物は遺伝子とタンパク質の発現を適切に変化させて対応する必要があります。 血糖値が低下すると、膵臓からグルカゴンというホルモンが分泌されます。 このホルモンは肝臓に、非炭水化物前駆体からグルコースを生成するために必要なタンパク質であるホスホエノールピルビン酸カルボキシキナーゼ(PEPCK)の生成を開始するよう信号を送ります。グルカゴンは、転写因子C/EBPαおよびC/EBPβを間接的に刺激してPEPCKプロモーターに結合することにより、この遺伝子の転写を誘導します。血糖値が高いと、膵臓はインスリンというホルモンを分泌します。PEPCK遺伝子には、その転写を阻害するインスリン応答性配列があります。

多細胞生物には、構造的および機能的に異なるさまざまな細胞タイプが含まれていますが、すべての細胞のDNAは同じ細胞に由来しています...

Education

JoVE Core

Molecular Biology

分子生物学

Unit 1

ユニット1

Gene Expression

遺伝子発現

KEY TERMS AND CONCEPTS

主要用語と概念

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 分子生物学は、明確で簡潔なアニメーション ビデオ レッスンを通じて細胞の分子プロセスを紹介します。さらに、科学者の実際のビデオでは、これらの概念の応用が現代の研究室での実際の実験を通じて実証されています。

How Cells Switch Genes On and Off

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