gene regulation

The Mechanism of Controlling Gene Expression in Organism

Collection

zero Useful+1

zero

This entry is made by Compilation and application of scientific encyclopedia entries of "Science Popularization China" to examine.

Gene regulation gene expression Mechanism. The main process of expression is gene Of Transcription and Messenger ribonucleic acid (mRNA). Gene regulation mainly occurs at three levels, namely ① DNA Horizontal regulation Transcription control and Translation control ；② microorganism The metabolic mode can be changed to adapt to environmental changes through gene regulation, which is generally temporary and reversible; ③ The gene regulation of multicellular organisms is cell differentiation 、 Morphogenesis and Ontogeny Such regulation is generally long-term and often irreversible. The study of gene regulation has a wide range of biological significance Genetic genetics And molecular genetics.

Chinese name: gene regulation
Foreign name: gene regulation
Concept: From DNA to protein The process of gene expression

Genus: The central subject of modern molecular biology research
Mechanism: Intrabiological control gene expression Mechanism of
Process: gene Of Transcription and Messenger ribonucleic acid translate

catalog

brief introduction

Announce

edit

The main process of expression is gene Of Transcription and Messenger ribonucleic acid (mRNA). Gene regulation mainly occurs at three levels, namely ① regulation at the DNA level Transcription control and Translation control ；② Microbes can change their metabolic mode to adapt to environmental changes through gene regulation, which is generally transient and reversible; ③ The gene regulation of multicellular organisms is cell differentiation 、 Morphogenesis And the basis of ontogeny, such regulation is generally long-term, and often irreversible. gene The study of regulation has a wide range of biological significance Genetic genetics And molecular genetics.

Through gene regulation, microorganisms can avoid excessive synthesis of amino acids nucleotide Such substances. If their Regulatory gene Mutation can produce a large amount of strain The use of these strains in the fermentation industry has greatly increased the production. stay genetic engineering Applying the principle of gene regulation in the research of gene expression (See Recombinant DNA technology ）Therefore, the theoretical discussion of gene regulation is also of practical significance.^[1]

brief history

Announce

edit

1900 F. Dinat Found in lactose and Galactose Cultured in Yeast There are galactose decomposing enzymes in cells, but there is no corresponding enzyme in yeast cells cultured in glucose medium. 1930 H. Karstrom Similar phenomena have been found in the research on bacteria, and the enzymes in biological cells are divided into Constitutive enzyme and Adaptive enzyme (also called Inducible enzyme ）The former is an enzyme that exists in all cases, and the latter is an enzyme that only exists in Inducer (generally, the substrate). 1938 J. Eugene use Law of mass action Explain the emergence of adaptive enzymes. 1946 French molecular biologist J. Mono Start research with Escherichia coli The phenomenon of induced synthesis of enzymes involved in lactose fermentation. American microbial geneticist in the same year J. Ledberg Etc Bacterial conjugation Then in 1948, the phenomenon of lactose Escherichia coli Mutant It is also isolated that β can decompose lactose in cells without contacting lactose- Galactose Type of glycosidase, i.e. loss of gene Mutants in regulatory capacity. On the basis of genetic research on Escherichia coli, J. Mono and F. Jacob The enzyme and a series of mutants in lactose fermentation of Escherichia coli continued to be extensively and deeply studied, and finally put forward lac Operon model , initiated the research of gene regulation mechanism. 1967 American scholar W. Gilbert Etc Repressor protein 1969 American molecular geneticist J. Shapiro The isolation of lactose operons has gradually made the study of gene regulation an important part of molecular genetics.^[1]

research method

Announce

edit

Screening mutant

This is prokaryote Methods widely used in, for example Lactose operon The screening of gene The composition of regulation capability, including Regulatory gene Mutation and Manipulating gene Mutants with mutations, and screening even if lactose or other Inducer β can not be synthesized in the presence of β- Galactose Glycosidase And so on.

Hormone induction

In advanced Eukaryote Medium, except in vitro somatic cell Other than (see Somatic cytogenetics ）, it is generally difficult to obtain the above Mutant 。 Therefore, the phenomenon that hormones can induce the production of specific proteins is often used to study the gene Regulation.

In vitro biochemical method

Eukaryote Of chromosome It is mainly composed of DNA and protein. So extract these ingredients separately and add other ingredients one by one before in vitro Transcription Or in vitro translation, which is also eukaryotic gene Research means often used in regulation research. Molecular hybridization Electron microscope observation and various general biochemical methods are important research means of gene regulation.

Recombinant DNA technology

many gene , including only one Developmental stage Active genes (see Gene library ）Can be isolated from the genome for research. application Sequence analysis of nucleic acids Technology can measure the genetic nucleotide Sequence. The mechanism of gene regulation can be directly understood by using in vivo and in vitro gene expression systems.^[1]

prokaryote

Announce

edit

DNA level gene Regulation Salmonella typhimurium (Salmoella typhimurium) has two codes Flagellum The protein genes H1 and H2 are not closely linked. There is one on one side of H2 Regulatory gene (H1 reporter gene, rh1), which encodes Repressor protein It acts on H1 and makes it not express. H2 gene On the other side of Inversion About 970 pairs long nucleotide The DNA sequence of Promoter （P）。 If the orientation of this sequence makes P adjacent to H2 and rh1, these two genes will Transcription , there is a kind of H2 gene in the cell Flagellin The repressor protein encoded by rh1 gene and rh1 gene acts on H1 gene and makes it not express, so the flagellum of bacteria is composed of H2 protein. When this sequence is inverted and takes another orientation, P is far away from H2 and rh1, so the flagellin encoded by H2 and Repressor protein When synthesis stops, H1 is expressed, and the bacterial flagellum becomes H1 protein. Flagellin is bacterial Flagellar antigen 。 The phenomenon that this antigen changes from one state (called phase) to another is called Phase transition 。

Similar phenomena also occur in Escherichia coli Mu-1 bacteriophage. Mu-1 bacteriophage chromosome There is a section about 3000 pairs nucleotide Of nucleotide sequence (called G), this sequence is often inverted. One of its orientations makes the phage shell proteins synthesized in cells are U and S. This phage can infect Escherichia coli, but cannot infect Citrobacter freundii. Its other orientation makes the shell proteins of phages synthesized in cells are U 'and S', which can infect Citrobacter freundii , but cannot infect E. coli.

Operon Model: bacterial and bacteriophage gene Regulation mostly occurs in Transcription At the level, the operon is the main gene regulatory unit of bacteria, that is Transcription unit 。 Coliform Lactose operon Is the first typical operon found, which includes Promoter （promoter,P）、 Manipulating gene (operator, lac O) and three Structural gene 。 Structural gene lac Z coding decomposition lactose Of β - galactosidase Lac Y codes lactose absorption β - galactoside permeating enzyme , lac A encodes β - galactoside acetyl Transferases 。 Next to lac Z is the manipulation gene lacO, which does not encode any protein, and it is located in another position Regulatory gene Lac I coded Repressor protein The joint of. Repressor protein is an allosteric protein. When there are lactose or other inducers in the cell, the repressor protein will combine with them. This combination makes the repressor protein conformation It cannot be combined on lac O, so Transcription So that the enzyme that absorbs and decomposes lactose can be produced (Fig. la); If there is no lactose or other inducer in the cell, the repressor protein will bind to lac O, thus preventing Promoter On P RNA polymerase The way forward makes transcription impossible (Fig. 1b). In this way gene Regulation can make bacteria lactose Enzymes that utilize lactose are synthesized in an environment where lactose is not available. One Operon It is a whole because: ① structurally, all genes of an operon are arranged together; ② Although an operon includes several Structural gene , but through Transcription It forms a single polygene mRNA ；③ The protein encoded by the structural gene belonging to an operon is always synthesized at a certain ratio; ④ Proximity in an operon Manipulating gene If some mutations occur in the structural gene of, the amount of protein encoded by the following series of genes will be reduced. This phenomenon is called Polarity effect , this Mutant be called Polar mutant ；⑤ There are Cis inverse position effect (See Complementarity ）。

lactose Operonic gene LacI encoded Repressor protein It plays a negative control role when it acts on gene manipulation Transcription The progress of is blocked. the other one Regulatory gene be called Cyclic adenosine receptor protein gene (cyclic AMP receiver protein gene, CRP) Cyclic adenylate (cAMP) binding and acting on the promoter in a binding state can promote transcription. This gene regulation belongs to Positive control 。 Glucose degradation products can reduce the concentration of cAMP in cells. After the concentration of cAMP is reduced, CRP protein will no longer bind to it, thus changing the conformation and losing the function of promoting transcription. This effect is called Glucose effect 。 Therefore, CRP protein is also called degradation product activator protein, CRP gene Also known as CAP gene 。 thus it can be seen lactose Operons are both negatively and positively controlled. This dual gene The regulation also meets the needs of bacteria: in the presence of lactose, bacteria need to synthesize, absorb and decompose lactose enzymes, but in the presence of glucose and lactose, bacteria do not need to use lactose anymore, so it is not necessary to synthesize and absorb and decompose lactose enzymes.

Similar gene regulation also acts on Anabolism 。 For example, when bacteria synthesize tryptophan or supply enough tryptophan from outside, tryptophan will interact with specific Regulatory gene Coded Repressor protein Binding repressor protein acts on Manipulating gene , thus Transcription If prevented, the enzyme necessary for tryptophan synthesis stops (Fig. 1c). stay Tryptophan When the number of free repressor proteins used for protein synthesis is reduced, the free repressor proteins will no longer act on the manipulation genes, so transcription can be carried out, enzymes will be synthesized, and tryptophan will be produced through the action of these enzymes (Fig. 1d). Tryptophan operon It is in the synthesis and metabolism of tryptophan gene The control unit is also a whole, with Lactose operon Same properties.

There are other forms of bacterial gene regulation, but lactose operon is its basic mode. Regulation methods include Positive control And negative control, and often positive and negative control acts on an operon at the same time. This multiple control is more effective than a single control. stay Escherichia coli The known operons in have exceeded 100.^[1]

Eukaryote

Announce

edit

Eukaryote Of gene Regulation ratio prokaryote It's much more complicated. This is because there are significant differences between the two types of organisms at three different levels: ① genetic material At the molecular level, the DNA content and the total number of genes in the eukaryotic genome are far higher than those in prokaryotes, and DNA is not chromosome The only component in, DNA and protein, and a small amount of RNA Nucleosome Is the basic unit of chromatin; ② At the cellular level, Eukaryotic cell Chromosomes of nuclear membrane Inside, Transcription And translation occur in the nucleus and cytoplasm respectively. These two processes are separated in time and space, and there is a rather complex RNA processing process between transcription and translation; ③ At the individual level, eukaryotes are different Histiocyte Formed, from the fertilized egg to the complete individual, there is a complex process of differentiation and development. In addition to those genes necessary to maintain the basic life activities of cells, genes in cells of other different tissues are always activated or suppressed in different space-time sequences. Related to differentiation and development gene The regulation mechanism is Genetic genetics The main contents of the study.

chromosome Gene regulation at the DNA level is achieved by changing the number and sequence structure of genes in the genome.

Chromatin loss

Some somatic cells lose some gene These genes will never be expressed, which is an extreme form of irreversible gene regulation.

Somatic cells during the development of some nematodes, protozoa and crustaceans are genetic material Loss phenomenon. Among these creatures, only germ cell Only then has retained the complete set of genes of the biological genome. For example, in Paralumbricoides equi (Ascaris megacephala) cleavage It was discovered in the early days of chromosome Loss of. The worker bee and queen bee yes diploid , and haploid They develop into drones. This can also be considered as a kind of gene regulation through chromosome loss.

Gene amplification

Another change gene The way of regulating gene expression by quantity is called gene amplification. Gene amplification means that cells produce a large number of Gene copy An extraordinary means of. Oocytes of some vertebrates and insects can specifically increase coding Ribosomal RNA DNA (rDNA) sequence. for example Xenopus Laevis (Xenopus laevis) oocyte Of rDNA in copy number It can increase sharply from 1500 at ordinary times to 2000000. This gene amplification only occurs in oocytes, and it is adapted to embryonic development For a large number of ribosomes. When the embryo stage begins, these chromosome The rDNA copy outside the cell loses its function and gradually disappears.

In addition to the specific amplification of rDNA Drosophila melanogaster Of Ovarian vesicle cells In Chorionic protein Genes in Transcription Specific amplification was also carried out before. By this means, cells can accumulate a large amount of Gene copy So as to produce a large number of fluff Membrane protein 。

DNA rearrangement

change gene The gene regulation mode related to the sequence structure of genes in group A. Mammalian immunoglobulin variable region The sequence with the constant region is encoded by different gene fragments. They are in the same chromosome However, they are far away from each other, and there are some DNA sequences encoding junction regions in the middle. During the maturation of antibody producing plasma cells, these three sequences Chromosome rearrangement And become a complete Transcription unit 。 because variable region gene There are many fragments, and different connection methods bring corresponding nucleotide The sequence changes, so this form of DNA rearrangement can produce a wide range of Immunoglobulin gene (See Immunogenetics).

In Saccharomyces cerevisiae cells Joint type Which of the two genes a and α is expressed depends on a special Transposable factor Shift of. But most of them have been found Eukaryote In terms of transposable factors, whether they participate in normal gene Regulation has not yet been finalized.

Transcription The gene regulation of eukaryotes at the level of Gene transcription Activity control does not involve changes in the number and structure of DNA sequence. Gene regulation at the transcriptional level can be achieved through different ways.

Chromatin activation

Chromatin in the state of condensation is called heterochromatization. Heterochromatic gene Of Transcription The activity decreased significantly. Eukaryote Can be changed chromosome The degree of heterochromatization of a region controls gene expression. female Mammalian cell The inactivation of one X chromosome in is the result of high heterochromatization (see Dose compensation effect ）。 When the gene is located near the heterochromatin region due to the change of position, the transcription will also be blocked (see Position effect ）。 A species of mealybug scale There are two types of individuals. The 10 chromosomes in the cells of one type of individuals are not heterochromatized, so they are all functional; In the other type of individual cells, 5 out of 10 chromosomes are highly heterochromatin, so they have no function. This creates a situation similar to that of bees. The diploid of bees is female, and the haploid is male; Here, the former is female, and the latter is male.

And Heterochromatization The opposite is chromatin activation. In activated chromatin, gene DNA is assembled to chromatin in a different way Nucleosome To enable RNA polymerase to Transcription DNA in chromatin. The research results show that gene expression Active chromatin DNA is much more sensitive to the degradation of endonuclease than chromatin without transcriptional activity. E.g. chicken Reticulum cell It can synthesize a large amount of globin, and contains Globin gene The chromatin DNA of Chromatin DNA will not be degraded in the chicken that does not synthesize globin Fallopian tube The chromatin DNA containing globin gene in cells is also not affected by this enzyme degradation 。 DNA in activated chromatin Superhelix The change of state is the premise of gene activation.

Modificatory effect

Eukaryotic cell The main way to modify DNA is cytosine (c) In position 5 methylation 。 5- Methyl cytosine Usually located next to guanine (G). It can be seen that GC order is most easily Methylation 。 At the DNA molecule Only Mother chain （ Template chain ）It is methylated. The methylation of the newborn DNA strand is carried out under the guidance of the parent strand. The results of analysis with restriction enzyme showed that Transcription More than 70% of the GC in DNA is methylated, while in DNA with high expression activity, only 20-30% of the GC sequence is methylated. This means DNA methylation The role of gene Regulation means.

Proteins can also be modified, including Acetylation 、 Phosphorylation Etc. except Histone and chromosome In addition to the firm binding of DNA, many Nonhistone It can also combine with DNA. The modification of these proteins can also change the way they combine with DNA, and change chromatin and Nucleosome And thus affect the transcriptional activity of genes. Some non histone components can also combine with hormones to activate some genes. In addition, RNA polymerase It can also be modified to change its activity.

gene induction

Bacterial metabolism Directly affected by the environment, its gene The signal of regulation often comes from environmental factors. multicellular The metabolism of higher organisms is less affected by the environment, and the signal of its gene regulation often comes from endogenous hormones.

In chironomus and Drosophila melanogaster (Drosophila), etc Dipteran insects Of Salivary gland Huge Polytene chromosome You can see the stripes with different characteristics. In each development stage of larva and pupa, some transverse stripes become loose and swollen, which is called Loose area 。 The emergence of loose areas has a certain time schedule, and each loose area disappears after a certain time. These sites are the sites where a large amount of RNA is synthesized, and Molecular hybridization It can be proved that the composition of the loose region has the property of mRNA. use Ecdysone Handling larvae or in vitro salivary glands , can induce some transverse lines to form loose areas, which means that some gene Is activated. This is hormone induced specific genes Transcription The most intuitive evidence.

In higher animals, injection of estrogen can promote the production of estrogen in liver cells of cock or chick Vitellogenin mRNA And synthesize vitellogenin; injection progesterone It can promote the production of oviduct cells of reptiles or birds Ovalbumin MRNA and synthesis of ovalbumin; Pituitary gland Propulsive action of anterior lobe Mammary hormone Mammalian Mammary gland cell synthesis casein 。

Steroid hormone The mechanism of action is generally believed to be that it first interacts with the recipient The protein combines to form a hormone receptor complex, and then this complex enters the nucleus chromosome There are some Nonhistone Under the condition of existence, the complex can be combined at a specific position of the chromosome, thus promoting a specific Gene transcription 。

RNA division

And prokaryote Different, Eukaryote There are three different RNA polymerase , they are responsible for different types of gene Transcription of. It is easy to see from the table that RNA Polymerase I and III Transcription The RNA of RNA is related to the basic function of all cell life activities translation, and only RNA polymerase II can transcribe Structural gene And further produce protein. Obviously, this division of labor reflects the significant differences in the expression mechanism of these three types of genes (see table). Different RNA polymerase can recognize different types of gene The mechanism of recognition is that each type of gene has a common or similar regulatory sequence. It has been proved in experiments in vivo and in vitro that Transcriptional starting point 25~30 upstream (5 ′ direction) nucleotide There is a relatively conservative section of about 8-10 nucleotides long, rich in A（ Adenine nucleotide ）And T（ Thymine nucleotide ）The nucleotide sequence of is called TATA frame. There is evidence that Transcription initiation Further upstream of RNA polymerase II, there are other nucleotide sequences also related to the normal activity of RNA polymerase II.

By RNA polymerase Ⅲ Transcription There is a segment in the 5SRNA gene of Transcription control The relevant order is about 30 base pairs long, and its existence is related to the Gene transcription The start of plays a controlling role. It has been proved that this sequence can specifically bind to a protein factor, which can guide RNA polymerase III to start transcription from about 50 base pairs upstream of its binding site.

Regulation in RNA Processing Eukaryote The RNA processing process of RNA mainly includes three steps: ① Add a Methylation Of Guanine nucleoside Acid, forming a so-called cap, m7GpppN (m7G is 7-methylguanine nucleoside, P is phosphoric acid, and N is the first nucleotide at the 5 'end of RNA). This process usually occurs before the completion of the new chain. ② stay Transcription Add Polyadenosine nucleotide (Poly A) tail. such Add tail Generally, the action does not occur directly on the 3 'end of the transcriptional primary product, but otherwise requires Endonuclease A new 3 'end is produced by the action of PA. ③ For with Intron The part of RNA The sequence must be cut off, followed by the two sides Exon The process of reconnecting is called splicing. Splicing is a very precise process, and its mechanism has not been clarified, but almost all introns have CT sequence at the 5 'boundary and AG sequence at the 3' boundary. The tail effect of poly A generally occurs before splicing, but it is not always the case. It is not clear about the various factors that affect this process, but the same one has been known gene The precursor mRNA of the transcript can be processed into several different mRNA.

Almost all Eukaryote The mRNA of all genes has a 5 'cap, but not all genes have 3' polya tails, and not all genes' mRNA must be spliced. According to the existence and complexity of the latter two processing processes Eukaryotic gene Of Transcription unit There are two types: one is simple genes that only encode one protein, and the other is complex transcription units that encode two or more proteins (Figure 2). The change on the tail part or splicing part at the 3 'end will make the same gene Finally, different protein products are formed. Figure 2a shows the pattern of different gene end products due to different tail positions of poly A, which belongs to adenovirus Late gene 、 mice immunoglobulin Heavy chain gene and a Polypeptide hormone Calcitonin Genes. Figure 2b shows the pattern that different splicing positions lead to different gene end products. So far, only Mammalian cell Virus (such as adenovirus 、 sv40 virus 、 Polyomavirus and Retrovirus This form of processing regulation is found in).

Translation control

Eukaryote The main form of translation control of RNA Stability. The capping effect of mRNA5 ′ end and its 3 ′ end polya Add tail It helps MRNA molecule Is stable. In some eukaryotes, mRNA does not act as a template immediately after entering the cytoplasm protein synthesis Instead, it combines with some proteins to form RNA protein (RNP) particles, and the half-life of mRNA in this state can be prolonged. silkworm Silk core protein gene It is a single copy, but in a few days a cell can synthesize up to 1010 fibroin molecules. This is because its mRNA molecule and protein combine to form RNP Particles and prolonging the life. It is estimated that one silk core protein gene can produce 105 mRNA molecules in a few days, so each mRNA molecule can be used as a template to synthesize 105 protein molecules. Some hormones can also stabilize mRNA. For example, add Prolactin It can accumulate 25000 copies of casein mRNA in 24 hours. During this period, the half-life of mRNA increased 20 times, but the synthesis of new mRNA only increased 2-3 times. If on Culture medium If prolactin is removed from the serum, 95% of casein mRNA will be lost within 48 hours. It can be seen that the main role of this hormone is to maintain casein m RNA Stability. The other two forms of translation control are the control of translation speed and selective translation, for example, Sea urchin The content and composition of mRNA in unfertilized eggs and fertilized eggs are the same, but the translation activity of fertilized eggs is at least 50 times higher. Different from this situation is the egg of clam, the total amount of protein synthesis of fertilized egg did not increase, but the biphasic translation of unfertilized and fertilized eggs in vitro Electrophoretic analysis The results showed that although their mRNA contents and types were the same, some proteins were specific to the eggs before fertilization, while others were specific to the eggs after fertilization.

post-translational control

There are few cases of post translation control. people say that Pituitary gland after Leaf cell Generated Adrenocorticotropic hormone and Fatty acid releasing hormone It is formed by the same original translation product through different processing. So far for Eukaryote gene The understanding of regulation is still at the stage of exploration, especially the understanding of gene regulation process of higher animals and plants is less, and a complete model cannot be formed. 1972 American scholar E. Davidson and R. J. Britton In the case of insufficient experimental facts, a gene regulation model of eukaryotes is proposed, which can also be used to explain a large number of Deoxyribonucleic acid The function of repeating the sequence.

According to this model, foreign signaling substances and sensing proteins combine to act on sensing genes, thus integrating the genome Transcription Produce mRNA of activating protein and further synthesize Activator protein These activating proteins act on Structural gene The previous acceptance order, so the structure Gene transcription And produce a series of enzymes or other proteins.

In this model, induction is assumed gene It is just some repetitive sequence, and it is assumed that each structural gene is distributed in chromosome At different locations. This model attempts to explain the function of repeat order and how genes distributed in different positions can be coordinated and controlled.

Once found in Eukaryote In the nucleus of RNA This fact is consistent with this model. This model is still a hypothesis to be fully verified. After this model was put forward, there appeared some hypotheses to modify this model, which can be used as the starting point for further research.^[1]

Practical significance

Announce

edit

Bacteria pass through gene Regulation can avoid excessive synthesis of amino acids nucleotide Etc. If people want to use bacteria to produce these substances, they must lose the role of gene regulation. In the general wild type bacteria, Repressor protein It acts on Manipulating gene And make Transcription stop it. There are two types Mutant It can make bacteria in a state of disinhibition and synthesis of excessive amino acids and other substances. One is the manipulation gene mutation type. Because of the structural change of the manipulation gene, the repressor protein cannot bind to it Operon They are always in active state; The other is the regulatory gene mutant, which encodes a repressor protein that cannot combine with the metabolic end product, so the repressor protein no longer acts on the manipulation gene and can also make the operon often active.

Structural analogs of amino acids (e.g 5-Methyltryptophan yes Tryptophan ) has the effect of inhibiting bacterial growth. Many anti analogs Mutant They belong to the above two types of mutants. In these mutant bacteria, the amount of enzymes directly related to the synthesis of this amino acid has increased, and this amino acid has also been synthesized in large quantities. In amino acids nucleotide Most of the strains used in the fermentation production are these mutants.^[1]

Novice on the road

Growth task Getting Started with Editing Edit Rule Edit by myself

I have questions

Content query Online Service Official post bar Feedback

Complaints and suggestions

Report bad information Failed to appeal through entries Complaint of infringement information Blocking query and unblocking

Jinggong Network Anbei No. 1100000200001