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

Każda komórka w organizmie wielokomórkowym posiada to samo DNA; jednak różne typy komórek mają zauważalne różnice strukturalne i funkcjonalne, które można przypisać zróżnicowanej ekspresji genów w komórce. 
Dodatkowo, określone komórki wyrażają różne geny w czasie z powodu zmian w komórce lub organizmie. Różnorodność wytwarzanych RNA i białek umożliwia komórkom wykonywanie ich unikalnych funkcji w odpowiednim czasie.
Komórki wątroby, zwane hepatocytami, wyrażają inny zestaw genów niż neurony.
Na przykład, komórki wątroby wytwarzają dehydrogenazę alkoholową, enzym, który rozkłada toksyczne alkohole na aldehyd octowy, który następnie może być dalej metabolizowany do produkcji dwutlenku węgla i wody. 
Natomiast neurony produkują neureksyny, grupę białek w mózgu, które pomagają przekazywać informacje z jednego neuronu do sąsiedniego. 
Komórki mają mechanizmy kontroli ekspresji genów na wielu etapach regulacyjnych przed, w trakcie i po transkrypcji i translacji. Jednak regulatory transkrypcji są powszechne, ponieważ zapobiegają syntezie transkryptów mRNA. 
Podczas rozwoju wątroby u ludzi, czynniki transkrypcyjne C/EBP α, C/EBP β i czynnik jądrowy hepatocytów-1 przyczyniają się do specyficznej dla wątroby ekspresji genów dehydrogenazy alkoholowej. 
Ekspresja genów jest również regulowana w odpowiedzi na środowisko zewnątrzkomórkowe. 
Gdy poziom glukozy we krwi spada, trzustka wydziela hormon glukagon. Po wystawieniu na działanie glukagonu, komórki wątroby wyrażają karboksykinazę fosfoenolopirogronianową, białko niezbędne do produkcji glukozy z prekursorów niewęglowodanowych.

<ol>
	<li>Alberts et al., wydanie 6; strony 369-374.</li>
	<li>Lodish et al., wydanie 8; strony 363-364</li>
	<li>Park, Edwards A. Austin L. Gurney, Steven E. Nizielski, Parvin Hakimi, Zhodan Caot, Antoon MoormanY i Richard W. Hanson. "Względne role białka wiążącego CCAAT/Enhancer-binding β i białka wiążącego element regulatorowy cAMP w kontrolowaniu transkrypcji genu karboksykinazy fosfoenolopirogronianowej (GTP)" Journal of Biological Chemistry 268, nr 1, (1993): 613-619</li>
</ol>

ekspresja genów specyficzna dla komórki

Cell Specific Gene Expression

Organizmy wielokomórkowe zawierają różnorodne strukturalnie i funkcjonalnie różne typy komórek, ale DNA we wszystkich komórkach pochodzi z tych samych komórek rodzicielskich. Różnice w komórkach można przypisać zróżnicowanej ekspresji genów. Komórki wątroby, których funkcje obejmują detoksykację krwi, wytwarzanie żółci w celu metabolizowania tłuszczów i syntezę białek niezbędnych do metabolizmu, muszą wykazywać ekspresję określonego zestawu genów, aby mogły wykonywać swoje funkcje. Ekspresja genów różni się również w zależności od etapów rozwoju. Przed różnicowaniem do komórek wątroby, komórki te wykazują ekspresję genów biorących udział w cyklu komórkowym, replikacji DNA i proliferacji. Na późniejszym etapie rozwoju geny zaangażowane w różnicowanie nabłonka i krzepnięcie krwi ulegają silnej ekspresji. Gdy komórki różnicują się w hepatocyty, wzrasta ekspresja genów zaangażowanych w funkcje specyficzne dla wątroby, na przykład tych zaangażowanych w metabolizm lipidów i regulację cholesterolu. Ekspresję genów można regulować na wielu etapach, w tym na transkrypcji, translacji, przetwarzaniu i transporcie RNA oraz modyfikacjach potranslacyjnych. Powszechnymi metodami regulacji ekspresji są czynniki, które wiążą się bezpośrednio z DNA w celu regulacji transkrypcji określonego genu. Ekspresja genów w wątrobie może być regulowana między innymi przez czynniki transkrypcyjne C/EBPα, C/EBPβ i czynnik jądrowy hepatocytów-1. Regulacja może nastąpić przed transkrypcją poprzez zmianę histonów zawartych w chromatynie. Modyfikacje te powodują albo rozluźnienie, albo zaciśnięcie struktury DNA, odpowiednio uniemożliwiając lub umożliwiając regulatorom transkrypcji dostęp do DNA. Różne typy komórek mają różne modyfikacje kowalencyjne i warianty histonów, co powoduje różnice w dostępności genów. Komórki podlegają zmianom środowiskowym i w odpowiedzi na bodźce zewnątrzkomórkowe wyrażają różne geny. Glukoza jest ważnym źródłem energii, a ponieważ jej stężenie w krwiobiegu ulega wahaniom, organizm musi reagować odpowiednimi zmianami w ekspresji genów i białek. Kiedy poziom glukozy we krwi spada, trzustka wydziela hormon glukagon. Hormon ten sygnalizuje wątrobie inicjowanie wytwarzania karboksykinazy fosfoenolopirogronianowej (PEPCK), białka niezbędnego do produkcji glukozy z prekursorów niewęglowodanowych. Glukagon indukuje transkrypcję tego genu poprzez pośrednią stymulację czynników transkrypcyjnych C/EBPα i C/EBPβ do wiązania się z promotorem PEPCK. Kiedy poziom glukozy we krwi jest wysoki, trzustka wydziela hormon insulinę; gen PEPCK ma sekwencję wrażliwą na insulinę, która hamuje jego transkrypcję.

Ekspresja genów specyficzna dla komórki

Organizmy wielokomórkowe zawierają różne strukturalnie i funkcjonalnie odrębne typy komórek, ale DNA we wszystkich komórkach pochodzi z tego samego ...

Education

JoVE Core

Molecular Biology

Biologia molekularna

Unit 1

Jednostka 1

Gene Expression

Ekspresja genów

KEY TERMS AND CONCEPTS

Kluczowe terminy i pojęcia

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 Molecular Biology showcases the molecular processes of the cell through clear and concise animated video lessons. Additionally, in scientist-in-action videos, these concepts' application is demonstrated through real experiments in modern laboratories.

How Cells Switch Genes On and Off

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