Transcriptional regulation
Encyclopedia
Transcriptional regulation is the change in gene expression
levels by altering transcription rates.
can be regulated by at least five mechanisms:
to describe a protein
involved in regulating gene expression
. It is usually bound to a DNA binding site
which is sometimes located near the promoter although this is not always the case. Regulatory proteins are often needed to be bound to a regulatory binding site to switch a gene on (activator
) or to shut off a gene (repressor
). Generally, as the organism grows more sophisticated, their cellular protein regulation becomes more complicated and indeed some human genes can be controlled by many activators and repressors working together.
that are generally located downstream from and near the promoter (normally part of the transcript). Activators bind to the upstream portion of the promoter, such as the CAP region (completely upstream from the transcript). A combination of activators, repressors and rarely enhancers (in prokaryotes) determines whether a gene is transcribed.
In eukaryotes, transcriptional regulation tends to involve combinatorial interactions between several transcription factors, which allow for a sophisticated response to multiple conditions in the environment. This permits spatial and temporal differences in gene expression. Eukaryotes also make use of enhancers
, distant regions of DNA that can loop back to the promoter. A major difference between eukaryotes and prokaryotes is the fact the eukaryotes have a nuclear envelope, which prevents simultaneous transcription and translation. RNA interference
also regulate gene expression in most eukaryotes, both by epigenetic modification of promoters and by breaking down mRNA.
to a receptor. Activation of g-protein-coupled receptors can have this effect; as can the binding of hormones to intra- or extracellular receptors.
This signal gives rise to the activation of a protein called a transcription factor
, and recruits other members of the "transcription machine
". Transcription factors generally simultaneously bind DNA as well as an RNA polymerase, as well as other agents necessary for the transcription process (HATs, scaffolding proteins, etc.). Transcription factors, and their cofactors, can be regulated through reversible structural alterations such as phosphorylation
or inactivated through such mechanisms as proteolysis
.
Transcription is initiated at the promoter site, as an increase in the amount of an active transcription factor binds a target DNA sequence. Other proteins, known as "scaffolding proteins" bind other cofactors and hold them in place. DNA sequences far from the point of initiation, known as enhancers, can aid in the assembly of this "transcription machinery." Histone
arms are acetylated, and DNA is transcribed into RNA.
Frequently, extracellular signals induce the expression of immediate early gene
s (IEGs) such as c-fos
, c-jun
, or AP-1
. These are in and of themselves transcription factors or components thereof, and can further influence gene expression.
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
levels by altering transcription rates.
Regulation of transcription
Regulation of transcription controls when transcription occurs and how much RNA is created. Transcription of a gene by RNA polymeraseRNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
can be regulated by at least five mechanisms:
- Specificity factorSpecificity factorSpecific Transcription Factors -Eukaryotic transcription begins with the formation of a pre initiation complex formed by the fusion of a group of general transcription factors...
s alter the specificity of RNA polymerase for a given promoter or set of promoters, making it more or less likely to bind to them (i.e. sigma factorSigma factorA sigma factor is a bacterial transcription initiation factor that enables specific binding of RNA polymerase to gene promoters. Different sigma factors are activated in response to different environmental conditions...
s used in prokaryotic transcriptionProkaryotic transcriptionProkaryotic transcription is the process in which messenger RNA transcripts of genetic material in prokaryotes are produced, to be translated for the production of proteins. Prokaryotic transcription occurs in the cytoplasm alongside translation. Unlike in eukaryotes, prokaryotic transcription and...
). - RepressorRepressorIn molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
s bind to non-coding sequences on the DNA strand that are close to or overlapping the promoter region, impeding RNA polymerase's progress along the strand, thus impeding the expression of the gene. - General transcription factorGeneral transcription factorGeneral transcription factors or basal transcription factors are protein transcription factors that have been shown to be important in the transcription of class II genes to mRNA templates...
s These transcription factors position RNA polymerase at the start of a protein-coding sequence and then release the polymerase to transcribe the mRNA. - ActivatorActivator (genetics)An activator is a DNA-binding protein that regulates one or more genes by increasing the rate of transcription. The activator may increase transcription by virtue of a connected domain which assists in the formation of the RNA polymerase holoenzyme, or may operate through a coactivator. A...
s enhance the interaction between RNA polymerase and a particular promoter, encouraging the expression of the gene. Activators do this by increasing the attraction of RNA polymerase for the promoter, through interactions with subunits of the RNA polymerase or indirectly by changing the structure of the DNA. - EnhancerEnhancer (genetics)In genetics, an enhancer is a short region of DNA that can be bound with proteins to enhance transcription levels of genes in a gene cluster...
s are sites on the DNA helix that are bound to by activators in order to loop the DNA bringing a specific promoter to the initiation complex.
Regulatory protein
Regulatory protein is a term used in geneticsGenetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
to describe a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
involved in regulating gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
. It is usually bound to a DNA binding site
DNA binding site
DNA binding sites are a type of binding site found in DNA where other molecules may bind. DNA binding sites are distinct from other binding sites in that they are part of a DNA sequence and they are bound by DNA-binding proteins...
which is sometimes located near the promoter although this is not always the case. Regulatory proteins are often needed to be bound to a regulatory binding site to switch a gene on (activator
Activator
Activator may mean:* Activator , a DNA-binding protein that regulates one or more genes by increasing the rate of transcription* Activator , a type of effector that increases the rate of enzyme mediated reactions...
) or to shut off a gene (repressor
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
). Generally, as the organism grows more sophisticated, their cellular protein regulation becomes more complicated and indeed some human genes can be controlled by many activators and repressors working together.
Prokaryotes vs. eukaryotes
In prokaryotes, regulation of transcription is needed for the cell to quickly adapt to the ever-changing outer environment. The presence or the quantity and type of nutrients determines which genes are expressed; in order to do that, genes must be regulated in some fashion. In prokaryotes, repressors bind to regions called operatorsOperator (biology)
In genetics, an operator is a segment of DNA to which a transcription factor protein binds. It is classically defined in the lac operon as a segment between the promoter and the genes of the operon. In the case of a repressor, the repressor protein physically obstructs the RNA polymerase from...
that are generally located downstream from and near the promoter (normally part of the transcript). Activators bind to the upstream portion of the promoter, such as the CAP region (completely upstream from the transcript). A combination of activators, repressors and rarely enhancers (in prokaryotes) determines whether a gene is transcribed.
In eukaryotes, transcriptional regulation tends to involve combinatorial interactions between several transcription factors, which allow for a sophisticated response to multiple conditions in the environment. This permits spatial and temporal differences in gene expression. Eukaryotes also make use of enhancers
Enhancer (genetics)
In genetics, an enhancer is a short region of DNA that can be bound with proteins to enhance transcription levels of genes in a gene cluster...
, distant regions of DNA that can loop back to the promoter. A major difference between eukaryotes and prokaryotes is the fact the eukaryotes have a nuclear envelope, which prevents simultaneous transcription and translation. RNA interference
RNA interference
RNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...
also regulate gene expression in most eukaryotes, both by epigenetic modification of promoters and by breaking down mRNA.
Examples
Examples:- When E. coli bacteria are subjected to heat stress, the σ32 subunit of its RNA polymerase changes such that the enzyme binds to a specialized set of promoters that precede genes for heat-shock response proteins.
- When a cell contains a surplus amount of the amino acid tryptophanTryptophanTryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
, the acid binds to a specialized repressor protein (tryptophan repressorTryptophan repressorTryptophan repressor is a transcription factor involved in controlling amino acid metabolism. It has been best studied in Escherichia coli, where it is a dimeric protein that regulates transcription of the 5 genes in the tryptophan operon...
). The binding changes the structural conformity of the repressor such that it binds to the operator region for the operon that synthesizes tryptophanTryptophanTryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
, preventing their expression and thus suspending production. This is a form of negative feedbackNegative feedbackNegative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
.
- In bacteria, the lac repressorLac repressorThe lac repressor is a DNA-binding protein which inhibits the expression of genes coding for proteins involved in the metabolism of lactose in bacteria. These genes are repressed when lactose is not available to the cell, ensuring that the bacterium only invests energy in the production of...
protein blocks the synthesis of enzymes that digest lactose when there is no lactose to feed on. When lactose is present, it binds to the repressor, causing it to detach from the DNA strand.
Inducible vs. repressible systems
Gene Regulation can be summarized as how they respond:- Inducible systems - An inducible system is off unless there is the presence of some molecule (called an inducer) that allows for gene expression. The molecule is said to "induce expression". The manner in which this happens is dependent on the control mechanisms as well as differences between prokaryotic and eukaryotic cells.
- Repressible systems - A repressible system is on except in the presence of some molecule (called a corepressor) that suppresses gene expression. The molecule is said to "repress expression". The manner in which this happens is dependent on the control mechanisms as well as differences between prokaryotic and eukaryotic cells.
Regulation of transcription machinery
In order for a gene to be expressed, several things must happen. First, there needs to be an initiating signal. This is achieved through the binding of some ligandLigand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
to a receptor. Activation of g-protein-coupled receptors can have this effect; as can the binding of hormones to intra- or extracellular receptors.
This signal gives rise to the activation of a protein called a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
, and recruits other members of the "transcription machine
Transcription machine
The transcription machine is a special purpose machine which is used for word or voice processing. This special device manages audio video recording to transcribe them into written or hard copy form...
". Transcription factors generally simultaneously bind DNA as well as an RNA polymerase, as well as other agents necessary for the transcription process (HATs, scaffolding proteins, etc.). Transcription factors, and their cofactors, can be regulated through reversible structural alterations such as phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
or inactivated through such mechanisms as proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
.
Transcription is initiated at the promoter site, as an increase in the amount of an active transcription factor binds a target DNA sequence. Other proteins, known as "scaffolding proteins" bind other cofactors and hold them in place. DNA sequences far from the point of initiation, known as enhancers, can aid in the assembly of this "transcription machinery." Histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
arms are acetylated, and DNA is transcribed into RNA.
Frequently, extracellular signals induce the expression of immediate early gene
Immediate early gene
Immediate early genes are genes which are activated transiently and rapidly in response to a wide variety of cellular stimuli. They represent a standing response mechanism that is activated at the transcription level in the first round of response to stimuli, before any new proteins are synthesized...
s (IEGs) such as c-fos
C-Fos
In the field of molecular biology and Genetics, c-Fos is a protein encoded by the FOS gene.-Structure and function:c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at...
, c-jun
C-jun
c-Jun is the name of a gene and protein that, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the...
, or AP-1
AP-1 (transcription factor)
In the field of molecular biology, the activator protein 1 is a transcription factor which is a heterodimeric protein composed of proteins belonging to the c-Fos, c-Jun, ATF and JDP families. It regulates gene expression in response to a variety of stimuli, including cytokines, growth factors,...
. These are in and of themselves transcription factors or components thereof, and can further influence gene expression.