File Name: regulation of transcription and gene expression in eukaryotes .zip
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 protein as the end product. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in ,  further developed in his article,  and expanded by the subsequent discoveries of reverse transcription    and RNA replication. The process of gene expression is used by all known life— eukaryotes including multicellular organisms , prokaryotes bacteria and archaea , and utilized by viruses —to generate the macromolecular machinery for life.
- 9.3: Regulation of Gene Expression in Eukaryotes
- Overview: Eukaryotic gene regulation
- Transcriptional regulation
- 19: Transcriptional regulation in eukaryotes
9.3: Regulation of Gene Expression in Eukaryotes
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 protein as the end product. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in ,  further developed in his article,  and expanded by the subsequent discoveries of reverse transcription    and RNA replication.
The process of gene expression is used by all known life— eukaryotes including multicellular organisms , prokaryotes bacteria and archaea , and utilized by viruses —to generate the macromolecular machinery for life. In genetics , gene expression is the most fundamental level at which the genotype gives rise to the phenotype , i.
The genetic information stored in DNA represents the genotype, whereas the phenotype results from the "interpretation" of that information. Such phenotypes are often expressed by the synthesis of proteins that control the organism's structure and development, or that act as enzymes catalyzing specific metabolic pathways. All steps in the gene expression process may be modulated regulated , including the transcription , RNA splicing , translation , and post-translational modification of a protein.
Regulation of gene expression gives control over the timing, location, and amount of a given gene product protein or ncRNA present in a cell and can have a profound effect on the cellular structure and function. Regulation of gene expression is the basis for cellular differentiation , development , morphogenesis and the versatility and adaptability of any organism.
Gene regulation may therefore serve as a substrate for evolutionary change. The production of a RNA copy from a DNA strand is called transcription , and is performed by RNA polymerases , which add one ribo nucleotide at a time to a growing RNA strand as per the complementarity law of the nucleotide bases.
In eukaryotes, transcription is performed in the nucleus by three types of RNA polymerases, each of which needs a special DNA sequence called the promoter and a set of DNA-binding proteins— transcription factors —to initiate the process see regulation of transcription below.
Transcription ends when the polymerase encounters a sequence called the terminator. While transcription of prokaryotic protein-coding genes creates messenger RNA mRNA that is ready for translation into protein, transcription of eukaryotic genes leaves a primary transcript of RNA pre-RNA , which first has to undergo a series of modifications to become a mature RNA. Types and steps involved in the maturation processes vary between coding and non-coding preRNAs; i.
The majority of eukaryotic pre-mRNAs consist of alternating segments called exons and introns. During the process of splicing, an RNA-protein catalytical complex known as spliceosome catalyzes two transesterification reactions, which remove an intron and release it in form of lariat structure, and then splice neighbouring exons together. In certain cases, some introns or exons can be either removed or retained in mature mRNA. This so-called alternative splicing creates series of different transcripts originating from a single gene.
Because these transcripts can be potentially translated into different proteins, splicing extends the complexity of eukaryotic gene expression and the size of a species proteome. Extensive RNA processing may be an evolutionary advantage made possible by the nucleus of eukaryotes. In prokaryotes, transcription and translation happen together, whilst in eukaryotes, the nuclear membrane separates the two processes, giving time for RNA processing to occur. In most organisms non-coding genes ncRNA are transcribed as precursors that undergo further processing.
While snoRNA part basepair with the target RNA and thus position the modification at a precise site, the protein part performs the catalytical reaction. After being exported, it is then processed to mature miRNAs in the cytoplasm by interaction with the endonuclease Dicer , which also initiates the formation of the RNA-induced silencing complex RISC , composed of the Argonaute protein. This is done either in the nucleoplasm or in the specialized compartments called Cajal bodies.
In eukaryotes most mature RNA must be exported to the cytoplasm from the nucleus. Specific exportin molecules are responsible for the export of a given RNA type. In some cases RNAs are additionally transported to a specific part of the cytoplasm, such as a synapse ; they are then towed by motor proteins that bind through linker proteins to specific sequences called "zipcodes" on the RNA.
The coding region carries information for protein synthesis encoded by the genetic code to form triplets. Each triplet of nucleotides of the coding region is called a codon and corresponds to a binding site complementary to an anticodon triplet in transfer RNA.
Transfer RNAs with the same anticodon sequence always carry an identical type of amino acid. Amino acids are then chained together by the ribosome according to the order of triplets in the coding region. In prokaryotes translation generally occurs at the point of transcription co-transcriptionally , often using a messenger RNA that is still in the process of being created. In eukaryotes translation can occur in a variety of regions of the cell depending on where the protein being written is supposed to be.
Major locations are the cytoplasm for soluble cytoplasmic proteins and the membrane of the endoplasmic reticulum for proteins that are for export from the cell or insertion into a cell membrane. Proteins that are supposed to be expressed at the endoplasmic reticulum are recognised part-way through the translation process. This is governed by the signal recognition particle —a protein that binds to the ribosome and directs it to the endoplasmic reticulum when it finds a signal peptide on the growing nascent amino acid chain.
Each protein exists as an unfolded polypeptide or random coil when translated from a sequence of mRNA into a linear chain of amino acids. This polypeptide lacks any developed three-dimensional structure the left hand side of the neighboring figure.
The polypeptide then folds into its characteristic and functional three-dimensional structure from a random coil. The resulting three-dimensional structure is determined by the amino acid sequence Anfinsen's dogma.
The correct three-dimensional structure is essential to function, although some parts of functional proteins may remain unfolded. Several neurodegenerative and other diseases are believed to result from the accumulation of misfolded proteins. Enzymes called chaperones assist the newly formed protein to attain fold into the 3-dimensional structure it needs to function. Secretory proteins of eukaryotes or prokaryotes must be translocated to enter the secretory pathway.
Newly synthesized proteins are directed to the eukaryotic Sec61 or prokaryotic SecYEG translocation channel by signal peptides. The efficiency of protein secretion in eukaryotes is very dependent on the signal peptide which has been used. Many proteins are destined for other parts of the cell than the cytosol and a wide range of signalling sequences or signal peptides are used to direct proteins to where they are supposed to be. In prokaryotes this is normally a simple process due to limited compartmentalisation of the cell.
However, in eukaryotes there is a great variety of different targeting processes to ensure the protein arrives at the correct organelle. Not all proteins remain within the cell and many are exported, for example, digestive enzymes , hormones and extracellular matrix proteins. In eukaryotes the export pathway is well developed and the main mechanism for the export of these proteins is translocation to the endoplasmic reticulum, followed by transport via the Golgi apparatus. Regulation of gene expression refers to the control of the amount and timing of appearance of the functional product of a gene.
Control of expression is vital to allow a cell to produce the gene products it needs when it needs them; in turn, this gives cells the flexibility to adapt to a variable environment, external signals, damage to the cell, and other stimuli. More generally, gene regulation gives the cell control over all structure and function, and is the basis for cellular differentiation , morphogenesis and the versatility and adaptability of any organism.
Numerous terms are used to describe types of genes depending on how they are regulated; these include:. Any step of gene expression may be modulated, from the DNA-RNA transcription step to post-translational modification of a protein.
The stability of the final gene product, whether it is RNA or protein, also contributes to the expression level of the gene—an unstable product results in a low expression level. In general gene expression is regulated through changes  in the number and type of interactions between molecules  that collectively influence transcription of DNA  and translation of RNA.
Regulation of transcription can be broken down into three main routes of influence; genetic direct interaction of a control factor with the gene , modulation interaction of a control factor with the transcription machinery and epigenetic non-sequence changes in DNA structure that influence transcription. Direct interaction with DNA is the simplest and the most direct method by which a protein changes transcription levels.
Genes often have several protein binding sites around the coding region with the specific function of regulating transcription. There are many classes of regulatory DNA binding sites known as enhancers , insulators and silencers. The mechanisms for regulating transcription are very varied, from blocking key binding sites on the DNA for RNA polymerase to acting as an activator and promoting transcription by assisting RNA polymerase binding.
The activity of transcription factors is further modulated by intracellular signals causing protein post-translational modification including phosphorylated , acetylated , or glycosylated.
These changes influence a transcription factor's ability to bind, directly or indirectly, to promoter DNA, to recruit RNA polymerase, or to favor elongation of a newly synthesized RNA molecule.
The nuclear membrane in eukaryotes allows further regulation of transcription factors by the duration of their presence in the nucleus, which is regulated by reversible changes in their structure and by binding of other proteins.
More recently it has become apparent that there is a significant influence of non-DNA-sequence specific effects on transcription. In general epigenetic effects alter the accessibility of DNA to proteins and so modulate transcription. In eukaryotes the structure of chromatin , controlled by the histone code , regulates access to DNA with significant impacts on the expression of genes in euchromatin and heterochromatin areas.
DNA methylation is a widespread mechanism for epigenetic influence on gene expression and is seen in bacteria and eukaryotes and has roles in heritable transcription silencing and transcription regulation. Methylation most often occurs on a cytosine see Figure. Methylation of cytosine primarily occurs in dinucleotide sequences where a cytosine is followed by a guanine, a CpG site.
The number of CpG sites in the human genome is about 28 million. Methylation of cytosine in DNA has a major role in regulating gene expression. Methylation of CpGs in a promoter region of a gene usually represses gene transcription  while methylation of CpGs in the body of a gene increases expression.
In a rat, contextual fear conditioning CFC is a painful learning experience. Just one episode of CFC can result in a life-long fearful memory. After CFC about genes have increased transcription often due to demethylation of CpG sites in a promoter region and about 1, genes have decreased transcription often due to newly formed 5-methylcytosine at CpG sites in a promoter region.
The pattern of induced and repressed genes within neurons appears to provide a molecular basis for forming the first transient memory of this training event in the hippocampus of the rat brain.
In particular, the brain-derived neurotrophic factor gene BDNF is known as a "learning gene. The majority of gene promoters contain a CpG island with numerous CpG sites. For example, in colorectal cancers about to genes are transcriptionally silenced by CpG island methylation see regulation of transcription in cancer. Transcriptional repression in cancer can also occur by other epigenetic mechanisms, such as altered expression of microRNAs.
In eukaryotes, where export of RNA is required before translation is possible, nuclear export is thought to provide additional control over gene expression. All transport in and out of the nucleus is via the nuclear pore and transport is controlled by a wide range of importin and exportin proteins. Expression of a gene coding for a protein is only possible if the messenger RNA carrying the code survives long enough to be translated.
In a typical cell, an RNA molecule is only stable if specifically protected from degradation. RNA degradation has particular importance in regulation of expression in eukaryotic cells where mRNA has to travel significant distances before being translated. As of , the miRBase web site,  an archive of miRNA sequences and annotations, listed 28, entries in biologic species.
The effects of miRNA dysregulation of gene expression seem to be important in cancer. The effects of miRNA dysregulation of gene expression also seem to be important in neuropsychiatric disorders, such as schizophrenia, bipolar disorder, major depression, Parkinson's disease, Alzheimer's disease and autism spectrum disorders.
Direct regulation of translation is less prevalent than control of transcription or mRNA stability but is occasionally used. Inhibition of protein translation is a major target for toxins and antibiotics , so they can kill a cell by overriding its normal gene expression control. Protein synthesis inhibitors include the antibiotic neomycin and the toxin ricin. Post-translational modifications PTMs are covalent modifications to proteins. Like RNA splicing, they help to significantly diversify the proteome.
These modifications are usually catalyzed by enzymes.
Overview: Eukaryotic gene regulation
In molecular biology and genetics , transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA transcription , thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology. The regulation of transcription is a vital process in all living organisms. It is orchestrated by transcription factors and other proteins working in concert to finely tune the amount of RNA being produced through a variety of mechanisms.
Several of these are described in this animation. Introduction. Initiation of transcription is the most important step in gene expression. Without the.
To understand how gene expression is regulated, we must first understand how a gene codes for a functional protein in a cell. The process occurs in both prokaryotic and eukaryotic cells, just in slightly different manners. Prokaryotic organisms are single-celled organisms that lack a cell nucleus, and their DNA therefore floats freely in the cell cytoplasm. To synthesize a protein, the processes of transcription and translation occur almost simultaneously. When the resulting protein is no longer needed, transcription stops.
NCBI Bookshelf. Cooper GM. The Cell: A Molecular Approach.
Of the approximately 30, genes in humans, any particular tissue will express a few at high abundance these are frequently tissue specific, e. The genes that are not expressed are frequently in an "inactive" region of the chromatin. The basic model is that genes that will not be expressed are kept in a default "off" state because they are packaged into a conformation of chromatin that prevents expression. Expression of a gene then requires opening of a chromatin domain, followed by the steps discussed in Part Three of this course: assembly of a transcription complex. Various active genes can be transcribed at distinctive rates, primarily determined by the differences in rate of initiation.
This section will consider submissions that focus on the analysis of gene expression levels and patterns, transcription mechanisms and the regulation of transcription. Hexaploid wheat is an important cereal crop that has been targeted to enhance grain micronutrient content including zinc Zn and iron Fe. In this direction, modulating the expression of plant transporters i
19: Transcriptional regulation in eukaryotes
The latest estimates are that a human cell, a eukaryotic cell, contains some 21, genes. Some of these are expressed in all cells all the time. These so-called housekeeping genes are responsible for the routine metabolic functions e. Some are expressed as a cell enters a particular pathway of differentiation. Some are expressed all the time in only those cells that have differentiated in a particular way.
For a cell to function properly, necessary proteins must be synthesized at the proper time. All cells control or regulate the synthesis of proteins from information encoded in their DNA. The process of turning on a gene to produce RNA and protein is called gene expression. Whether in a simple unicellular organism or a complex multi-cellular organism, each cell controls when and how its genes are expressed. For this to occur, there must be a mechanism to control when a gene is expressed to make RNA and protein, how much of the protein is made, and when it is time to stop making that protein because it is no longer needed. The regulation of gene expression conserves energy and space.
As shown in the animation, this process involves many different proteins. Some of these proteins are general transcription factors that recruit RNA polymerase to the gene. Other proteins, such as activators, repressors, and mediators, are transcription factors that regulate the action of RNA polymerase. Skip to main content. Share This. Details Key Terms.
NCBI Bookshelf. Cooper GM. The Cell: A Molecular Approach. Sunderland MA : Sinauer Associates; Although the control of gene expression is far more complex in eukaryotes than in bacteria, the same basic principles apply.
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