In
molecular genetics
Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...
, a repressor is a
DNA- or RNA-binding protein that inhibits the
expression
Expression may refer to:
Linguistics
* Expression (linguistics), a word, phrase, or sentence
* Fixed expression, a form of words with a specific meaning
* Idiom, a type of fixed expression
* Metaphorical expression, a particular word, phrase, o ...
of one or more genes by binding to the
operator or associated
silencers. A DNA-binding repressor blocks the attachment of
RNA polymerase to the
promoter, thus preventing
transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
of the genes into
messenger RNA. An RNA-binding repressor binds to the mRNA and prevents
translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
of the mRNA into protein. This blocking or reducing of expression is called repression.
Function
If an
inducer
In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely:
*By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...
, a molecule that initiates the gene expression, is present, then it can interact with the repressor protein and detach it from the operator.
RNA polymerase then can
transcribe
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
the message (expressing the gene). A
co-repressor In the field of molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DN ...
is a molecule that can bind to the repressor and make it bind to the operator tightly, which decreases transcription.
A repressor that binds with a co-repressor is termed an ''aporepressor'' or ''inactive repressor''. One type of
aporepressor is the
trp repressor
Tryptophan repressor (or trp 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 t ...
, an important metabolic protein in bacteria. The above mechanism of repression is a type of a feedback mechanism because it only allows transcription to occur if a certain condition is present: the presence of specific
inducer
In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely:
*By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...
(s). In contrast, an active repressor binds directly to an operator to repress gene expression.
While repressors are more commonly found in prokaryotes, they are rare in eukaryotes. Furthermore, most known eukaryotic repressors are found in simple organisms (e,g. yeast), and act by interacting directly with activators. This contrasts prokaryotic repressors which can also alter DNA or RNA structure.
Within the eukaryotic genome are regions of DNA known as
silencers. These are DNA sequences that bind to repressors to partially or fully repress a gene. Silencers can be located several bases upstream or downstream from the actual promoter of the gene. Repressors can also have two binding sites: one for the silencer region and one for the
promoter. This causes chromosome looping, allowing the promoter region and the silencer region to come in proximity of each other.
Examples of Repressors
''lac'' operon repressor
The ''lacZYA'' operon houses genes encoding proteins needed for lactose breakdown.
[Slonczewski, Joan, and John Watkins. Foster. Microbiology: An Evolving Science. New York: W.W. Norton &, 2009. Print.] The ''lacI'' gene codes for a protein called "the repressor" or "the lac repressor", which functions to repressor of the lac operon.
The gene ''lacI'' is situated immediately upstream of ''lacZYA'' but is transcribed from a ''lacI'' promoter.
The ''lacI'' gene synthesizes LacI repressor protein. The LacI repressor protein represses ''lacZYA'' by binding to the operator sequence ''lacO''.
The ''lac'' repressor is
constitutively expressed
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
and usually bound to the
operator region of the
promoter, which interferes with the ability of
RNA polymerase (RNAP) to begin transcription of the ''lac'' operon.
In the presence of the
inducer
In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely:
*By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...
allolactose
Allolactose is a disaccharide similar to lactose. It consists of the monosaccharides D-galactose and D-glucose linked through a β1-6 glycosidic linkage instead of the β1-4 linkage of lactose. It may arise from the occasional transglycosylati ...
, the repressor changes conformation, reduces its DNA binding strength and dissociates from the operator DNA sequence in the promoter region of the lac operong. RNAP is then able to bind to the promoter and begin transcription of the ''lacZYA'' gene.
''met'' operon repressor
An example of a repressor protein is the
methionine repressor MetJ. MetJ interacts with
DNA bases via a ribbon-helix-helix (RHH) motif. MetJ is a
homodimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
consisting of two
monomers
In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization.
Classification
Mo ...
, which each provides a
beta ribbon and an
alpha helix. Together, the beta ribbons of each monomer come together to form an
antiparallel beta-sheet
The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a ge ...
which binds to the DNA
operator ("Met box") in its major groove. Once bound, the MetJ
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ...
interacts with another MetJ dimer bound to the complementary strand of the operator via its alpha helices. AdoMet binds to a pocket in MetJ that ''does not'' overlap the site of DNA binding.
The Met box has the DNA sequence AGACGTCT, a
palindrome (it shows
dyad symmetry In genetics, dyad symmetry refers to two areas of a DNA strand whose base pair sequences are inverted repeats of each other. They are often described as palindromes.
For example, the following shows dyad symmetry between sequences GAATAC and GTATT ...
) allowing the same sequence to be recognized on either strand of the DNA. The junction between C and G in the middle of the Met box contains a
pyrimidine-purine step that becomes
positively supercoiled forming a kink in the
phosphodiester
In chemistry, a phosphodiester bond occurs when exactly two of the hydroxyl groups () in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. The "bond" involves this linkage . Discussion of phosphodiesters is d ...
backbone. This is how the protein checks for the recognition site as it allows the DNA duplex to follow the shape of the protein. In other words, recognition happens through indirect readout of the structural parameters of the DNA, rather than via specific base sequence recognition.
Each MetJ
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ...
contains two binding sites for the
cofactor S-Adenosyl methionine
''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...
(SAM) which is a product in the biosynthesis of methionine. When SAM is present, it binds to the MetJ protein, increasing its affinity for its cognate operator site, which halts transcription of genes involved in methionine synthesis. When SAM concentration becomes low, the repressor dissociates from the operator site, allowing more methionine to be produced.
L-arabinose operon repressor
The
L-arabinose
Arabinose is an aldopentose – a monosaccharide containing five carbon atoms, and including an aldehyde (CHO) functional group.
For biosynthetic reasons, most saccharides are almost always more abundant in nature as the "D"-form, or structural ...
operon houses genes coding for arabinose-digesting enzymes. These function to break down arabinose as an alternative source for energy when glucose is low or absent.
The
operon
In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...
consists of a regulatory repressor gene (araC), three control sites (ara02, ara01, araI1, and araI2), two promoters (Parac/ParaBAD) and three structural genes (araBAD). Once produced, araC acts as repressor by binding to the araI region to form a loop which prevents
polymerases from binding to the promotor and
transcribing
Transcription in the linguistic sense is the systematic representation of spoken language in written form. The source can either be utterances (''speech'' or ''sign language'') or preexisting text in another writing system.
Transcription shoul ...
the structural genes into proteins.
In the absence of
Arabinose and araC (repressor), loop formation is not initiated and structural gene expression will be lower. In the absence of Arabinose but presence of araC, araC regions form dimers, and bind to bring ara02 and araI1 domains closer by loop formation. In the presence of both Arabinose and araC, araC binds with the arabinose and acts as an activator. This conformational change in the araC no longer can form a loop, and the linear gene segment promotes
RNA polymerase recruitment to the structural araBAD region.
+
Flowing Locus C (Epigenetic Repressor)
The
FLC operon is a conserved eukaryotic locus that is negatively associated with flowering via repression of genes needed for the development of the
meristem
The meristem is a type of tissue found in plants. It consists of undifferentiated cells (meristematic cells) capable of cell division. Cells in the meristem can develop into all the other tissues and organs that occur in plants. These cells conti ...
to switch to a floral state in the plant species ''
Arabidopsis thaliana''. FLC expression has been shown be regulated by the presence o
FRIGIDA and negatively correlates with decreases in temperature resulting in the prevention of
vernalization
Vernalization (from Latin ''vernus'', "of the spring") is the induction of a plant's flowering process by exposure to the prolonged cold of winter, or by an artificial equivalent. After vernalization, plants have acquired the ability to flower, ...
. The degree to which expression decreases depends on the temperature and exposure time as seasons progress. After the downregulation of FLC expression, the potential for flowering is enabled. The regulation of FLC expression involves both genetic and
epigenetic factors such as
histone methylation and
DNA methylation. Furthermore, a number of genes are
cofactors act as negative transcription factors for FLC genes. FLC genes also have a large number of homologues across species that allow for specific adaptations in a range of climates.
See also
*
Promoter (biology)
*
Activator (genetics)
*
Operon
In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...
*
Regulation of gene expression
*
Transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
*
lac repressor
The ''lac'' repressor (LacI) is a DNA-binding protein that 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 ...
*
P300/CBP
*
Glossary of gene expression terms
A glossary (from grc, γλῶσσα, ''glossa''; language, speech, wording) also known as a vocabulary or clavis, is an alphabetical list of terms in a particular domain of knowledge with the definitions for those terms. Traditionally, a glos ...
References
External links
*
{{Transcription
DNA-binding proteins
Gene expression