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- regulation of gene expression in prokaryotes and eukaryotes pdf
- regulation of gene expression in prokaryotes and eukaryotes pdf
Regulation of gene expression is achieved by the presence of cis regulatory elements; these signatures are interspersed in the noncoding region and also situated in the coding region of the genome. These elements orchestrate the gene expression process by regulating the different steps involved in the flow of genetic information.
Current chapter describes the structural and functional elements present in the coding and noncoding region of the genome. Further we discuss role of regulatory elements in regulation of gene expression in prokaryotes and eukaryotes. Finally, we also discuss DNA structural properties of regulatory regions and their role in gene expression. Identification and characterization of cis regulatory elements would be useful to engineer the regulation of gene expression.
Genome, the blue print of life, is essentially comprised of coding genes and noncoding regulatory regions and other repetitive sequences DNA. Genetic information is embedded in the form of coding regions genes that encode proteins.
This flow of information from gene to proteins is a multistep pathway viz. Control of this flow of information is crucial for fate of the cell and this phenomenon is known as the regulation of the gene expression. The function of the cell is determined by the amount and type of the RNA and protein molecules that is achieved by the regulation of the gene expression.
There are various steps involved in this flow of information process such as chromatin domain organization, transcription initiation, elongation and termination , post-transcriptional modification, RNA export exclusive for eukaryotes , translation and mRNA degradation. Among all these different regulated stages of gene expression transcription initiation is the most utilized point of regulation.
Transcription event is coupled with the translation process in the case of prokaryotes due to availability of ribosomes in the same compartment due to lack of nucleus. However, transcription process is far more complicated in case of eukaryotes due to involvement of additional steps that are RNA splicing and RNA export.
These additional steps provide extra stages for the regulation of gene expression process in eukaryotes. Regulation of gene expression is achieved by harnessing the regulatory elements, located in the noncoding as well as coding regions of the genome.
Current chapter focuses on the different structural and functional elements present in the coding regions genes and noncoding regions regulatory regions , which are utilized by the cell to regulate the gene expression process. Genes are the repositories for primary information content of inheritance in genome and their expression determines the phenotypes, which in turn decides future of the cell in multicellular organisms.
Functioning of gene products viz. Eukaryotic genomes are mostly comprised of compositional properties repetitive sequences, codon usage bias, mutational information, etc. Processing of the transcript is an important phase in the gene expression process, which also provides additional level of regulation in eukaryotes.
Transcription and translation events are coupled in prokaryotes due to the availability of ribosomes to the mRNA while transcript undergoes several levels of processing in nucleus and finally processed transcripts are exported to the cytoplasm for translation in eukaryotes. Complexity in the gene structure results into the phenotypic diversity and this complexity arises from the occurrence and arrangement of the noncoding elements interspersing the coding region. Gene expression diversification is achieved by the presence of trailer sequences known as untranslated region UTR and intervening noncoding sequences known as introns [ 2 ].
These elements exert several direct and indirect functions. The IRES mediated translational regulation occurs under certain stress conditions such as cellular stress, nutritional stress, mitotic stress etc. Antibiotic resistance in the pathogenic bacteria is also found to be associated with uORFs mediated regulation [ 23 ]. In a recent study, fusion of uORF in the upstream of the auto-activated immune receptor gene developed the resistance to the plant diseases in Arabidopsis and rice [ 24 ]. The poly A binding proteins PABP , specific class of regulatory proteins nuclear and cytoplasmic binds to the poly A tail and perform different regulatory functions like stability of mRNA, export and decay of the mRNA.
These proteins play vital role in gene regulation [ 32 , 33 , 34 , 35 ]. There are four different types of introns based on different splicing mechanisms. Spliceosomal introns are the foremost discovered and well characterized introns, which are excised by spliceosome, a ribonucleoprotein complex [ 36 , 37 ]. Similarly, group II introns are large autocatalytic ribozymes widely present in the mitochondria, chloroplast, plants, fungi, yeast and many bacteria, play major role in genome evolution [ 43 , 44 , 45 , 46 ].
The tRNA introns widely present in all domains of life are exceptionally different as enzymes are involved in the removal of intron and in the joining of the two halves [ 47 , 48 , 49 ]. Gene regulation is modulated to a great extent by count or number, length and position of the introns and they have several direct and indirect biological functions [ 50 ].
Multiple protein isoforms of the same gene are derived from the regulated alternative splicing process in eukaryotes [ 51 , 52 , 53 , 54 ].
Introns modulate gene expression either by the presence of transcriptional regulatory elements or by intron mediated enhancements [ 55 , 56 , 57 ]. Introns also regulate the gene expression by mediating the chromatin assembly chromatin structure modulation and controlling the mRNA export [ 58 , 59 , 60 , 61 ]. Apart from these direct biological functions, introns also exert indirect influence, for example position and length of the intron in the gene have potential role in the regulation of the expression level of the transcript [ 62 , 63 , 64 , 65 ].
Promoters are stretch of genomic sequences where assembly of transcription machinery RNAP and other accessory proteins takes place prior to initiation of transcription. Although prokaryotic and eukaryotic polymerase shares functional similarity, promoter architecture differs in complexity [ 66 ]. On the other hand, complexity of promoter architecture in eukaryotes increases from yeast to mammals. Eukaryotic promoters can be broadly classified in to three categories such as core, distal and proximal.
The core promoter approximately 50 nucleotide sequence is a platform where assembly of RNA polymerase and associated general transcription factors GTFs , collectively referred as pre- initiation complex PIC takes place [ 68 , 69 ]. Apart from these, core promoter regions also consist of Inr element and may also contain downstream elements like downstream promoter element DPE , motif ten element MTE in humans [ 71 ].
List of core promoter elements and factors associated with them [ 72 , 73 ]. Proximal promoters are located in the immediate upstream up to a few hundred base pairs of core promoter, are comprised of GC box, CAAT box, cis -regulatory modules CRM etc. CpG islands are stretch of short DNA sequences, which are rich in GC content located in the upstream of house keeping and other regulated gene promoters [ 72 , 73 ].
Proximal promoters mostly work as tethering element for distal promoters instead of acting as direct activators. On the other hand, distal promoters work from long distance. Enhancers, silencers and insulators are present in the distal promoter regions. Multiple enhancers associated with single gene and single enhancer activating multiple genes provides additional level of diversity in phenotypes. In contrast to other regulators, enhancers exert their effects over tens of kilobases of DNA [ 75 , 76 ].
Silencers are sequence specific elements where negative transcription factors bind to down regulate the gene expression [ 77 ]. Insulators are also referred to as boundary elements which block the effect of transcriptional activity of neighboring genes [ 77 , 78 ]. The locations and strengths of transcription factor and RNAP binding sites, also known as cis -regulatory elements and list of all nucleosome-binding sites are collectively defining the promoter structure.
Nucleosomes are not only involved in the packaging of DNA but also bring order to the eukaryotic genome by regulating replication and transcription [ 79 , 80 ]. Nucleosomes provide the first line of defense to avoid the unwanted transcription initiation. Nucleosome positioning is the probability of finding nucleosome at given genomic location relative to the surrounding locations while nucleosome occupancy refers to the average number nucleosomes present at the given genomic location in a given population of cells [ 83 , 84 ].
Cellular gene expression is the final outcome of nucleosome dynamics, which itself depends on a complex interplay between nucleosome positioning and occupancy [ 85 , 86 , 87 ]. DNA sequence not only determines the distinct or base specific interactions but also determines the overall conformational shape, which is recognized by different proteins in case of non-base specific interactions [ 88 ].
The higher DNA binding specificity is achieved by combing different readout mechanisms by DNA binding proteins, with DNA shape playing an important role in gene regulation and genome organization [ 89 ]. The DNA sequence dependent structural properties can be roughly divided in to two categories, conformational and physiochemical [ 90 ].
Conformational properties represent the static DNA structure, which are influenced by geometry of base pair steps described by translational shift, slide and rise and rotational tilt, roll and twist parameters [ 91 ]. These also determine variation in the major and minor groove dimensions, which are crucial for DNA protein interactions.
The physiochemical properties refer to the dynamic DNA structural properties such as persistence length, stress induced duplex destabilization, DNA duplex stability, protein induced bendability and intrinsic curvature etc. Structural properties of given DNA sequence can be calculated using different di, tri tetra nucleotide models reported in experimental as well as theoretical studies.
These models provide property values lookup tables for different oligonucleotides and using these values and appropriate length sliding window , a given DNA sequence can be converted in to a series of numerical values referred to as a structural property profile. These profiles of given DNA sequence show variation in the structural property over the different regions of the sequence Figure 3. An average structural property profile is calculated by taking mean of the feature value over all positions by aligning the different sequences [ 92 ].
DNA structural features such as low stability, protein induced bendability and intrinsic curvature are consistently observed in the prokaryotic and eukaryotic promoters Figure 4 [ 93 , 94 , 95 , 96 ].
Promoter regions of different categories of transcripts primary, internal, antisense and noncoding RNA present in prokaryotic transcriptome show distinctly different DNA structural features [ 97 ]. Moreover, promoter regions of orthologous genes show conserved DNA structural properties in prokaryotes and plants [ 98 , 99 , ].
These findings suggest that the DNA structural properties of promoter regions are conserved across the various classes of organisms. Schematic illustration showing DNA structural properties profile example shown for DNA duplex stability using values for di, tri, tetra nucleotide etc. Stability profile shows variation depending on the DNA sequence.
Transcription factors TFs , proteins that bind to specific regulatory sequences cis -regulatory elements or CRE are the key regulators of transcription [ ]. The complex gene regulation in eukaryotes is a consequence of the large number of transcription factors available and localization of cis -regulatory elements. A variation in the copy number of mRNA or protein molecules for a given gene in cell is referred as gene expression noise.
It is largely under the control of regulatory DNA since it is linked with the promoter structure. TATA box with variable strength, transcription factor binding sites count, strength and their position in the promoter and nucleosome binding sites in the regulatory region have enormous effect on gene expression noise in eukaryotes [ ].
Though transcriptional regulation is quite well understood at molecular level, very little is known about gene expression noise in the case of prokaryotes.
Transcription factors and inducer molecules play a major role in gene regulation process. Additionally, genome condensation assisted by nucleoid associated proteins and DNA supercoiling also play a vital role in gene regulation in bacteria. Gene expression noise is essential for achieving phenotypic heterogeneity and it has been found to be universal in nature.
Nucleosome organization in the genome has been found to be closely associated with the gene expression and its variability [ 82 , 84 , 85 ]. Genes with dissimilar expression levels tend to have sequences with different structural features in order to attain the required nucleosome organization [ , , ]. Plasticity of gene expression, also known as gene expression variability is crucial for cell survival, is closely linked with the DNA structural properties of promoter region in S.
Promoters of genes with low plasticity less responsive are less stable, less bendable and lower nucleosome occupancy compared to the promoters of genes with high plasticity high responsive [ , ]. It has been found that promoter regions associated with high gene expression are less stable, less bendable and more curved as compare to the genes associated with low gene expression as seen from Figure 5. Intrinsic curvature was found to be most significant property which is distinctly present in the promoter regions associated with high gene expression as compared to those with low gene expression across all organisms [ 97 ].
Hence estimation and characterization of DNA structural features of promoter regions could be very informative in analyzing the expression of associated gene. Violin plot of four DNA structural property values in the promoter regions to 0 nucleotide with respect to TSS at 0 associated with high and low gene expression in six different prokaryotes. The x-axis shows the probability density while y-axis represents the DNA structural feature value.
The growing plethora of genomic information in the form of whole genome sequences requires its annotation to make sense of it. Mere delineation of coding sequences gene identification is not enough to get complete understanding of functional genomics since regulation of gene expression orchestrates the fate of cells. Gene expression regulation depends on different regulatory elements localized in the noncoding and coding region of the genome.
Identification and characterization of these regulatory elements is the next level of challenge in the genome annotation process.
regulation of gene expression in prokaryotes and eukaryotes pdf
Multiple proteins binding together to increase specificity. Besides, the regulation of the prokaryotic gene expression occurs at the transcriptional level while the regulation of the eukaryotic gene expression can occur at epigenetic level, transcriptional level, post-transcriptional level, translational level, and post-translational level. The effect of a gene regulatory protein is amplified when it is combined with other proteins. The genes in eukaryotes are also regulated in more or less the same manner as that of prokaryotes, but the regulation is mostly positive and very rarely negative regulation is seen. The Control of Gene Expression 1. In prokaryotes, regulatory mechanisms are generally simpler than those found in eukaryotes. Transcriptional Regulation of Gene Expression in Eukaryotes: The variation in the rate of transcription often regulates gene expression.
Regulation of gene expression is achieved by the presence of cis regulatory elements; these signatures are interspersed in the noncoding region and also situated in the coding region of the genome. These elements orchestrate the gene expression process by regulating the different steps involved in the flow of genetic information. Current chapter describes the structural and functional elements present in the coding and noncoding region of the genome. Further we discuss role of regulatory elements in regulation of gene expression in prokaryotes and eukaryotes. Finally, we also discuss DNA structural properties of regulatory regions and their role in gene expression. Identification and characterization of cis regulatory elements would be useful to engineer the regulation of gene expression.
To understand how gene expression is regulated, we must first understand how a gene becomes a functional protein in a cell. The process occurs in both prokaryotic and eukaryotic cells, just in slightly different fashions. Because prokaryotic organisms lack a cell nucleus, the processes of transcription and translation occur almost simultaneously. When the protein is no longer needed, transcription stops. As a result, the primary method to control what type and how much protein is expressed in a prokaryotic cell is through the regulation of DNA transcription into RNA.
regulation of gene expression in prokaryotes and eukaryotes pdf
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.
NCBI Bookshelf. Cooper GM. The Cell: A Molecular Approach. Sunderland MA : Sinauer Associates;
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Все звонки принимались единственным оператором на двенадцатиканальный терминал Коренсо-2000. Телефонистка, державшая трубку у уха, мгновенно поднялась и поклонилась, увидев босса. - Садитесь! - рявкнул Нуматака. Она опустилась на стул. - В четыре сорок пять ко мне на личный телефон поступил звонок. Вы можете сказать, откуда звонили? - Он проклинал себя за то, что не выяснил этого раньше. Телефонистка нервно проглотила слюну.
Как и многие другие сотрудники АНБ, он использовал разработанную агентством программу Мозговой штурм - безопасный способ разыгрывать сценарий типа Что, если?. на защищенном от проникновения компьютере. Мозговой штурм был своего рода разведывательным экспериментом, который его создатели называли Симулятором причин и следствий. Сначала он предназначался для использования в ходе избирательных кампаний как способ создания в режиме реального времени моделей данной политической среды. Загруженная громадным количеством информации программа создавала паутину относительных величин - гипотетическую модель взаимодействия политических переменных, включая известных политиков, их штабы, личные взаимоотношения, острые проблемы, мотивации, отягощенные такими факторами, как секс, этническая принадлежность, деньги и власть. Пользователь имел возможность создать любую гипотетическую ситуацию, и Мозговой штурм предсказывал, как эта ситуация повлияет на среду.
- Где, черт возьми, регистратура. За едва заметным изгибом коридора Беккер услышал голоса. Он пошел на звук и уткнулся в стеклянную дверь, за которой, судя по доносящемуся оттуда шуму и гвалту, происходило нечто вроде драки.
- Так скажите же мне. Стратмор задумался и тяжело вздохнул. - Пожалуйста, сядь, Сьюзан. У нее был совершенно растерянный вид.
Это была хорошая весть: проверка показала код ошибки, и это означало, что Следопыт исправен. Вероятно, он отключился в результате какой-то внешней аномалии, которая не должна повториться. Код ошибки 22.
Информация, которую он выдал… Она резко подняла голову. Возможно ли. Информация, которую он выдал. Если Стратмор получил от Следопыта информацию, значит, тот работал. Она оказалась бессмысленной, потому что он ввел задание в неверной последовательности, но ведь Следопыт работал.
Сразу же? - усомнилась Сьюзан. - Каким образом. Даже если Цифровая крепость станет общедоступной, большинство пользователей из соображений удобства будут продолжать пользоваться старыми программами.
Что бы он ни делал - спал, стоял под душем, ел, - ключ всегда при нем, в любую минуту готовый для опубликования. - На пальце? - усомнилась Сьюзан. - У всех на виду. - Почему бы и. Испания отнюдь не криптографический центр мира.
Но, сэр, мутация… - Немедленно! - крикнул Стратмор. Чатрукьян некоторое время смотрел на него, лишившись дара речи, а потом бегом направился прочь из шифровалки. Стратмор повернулся и с удивлением увидел Хейла. Сьюзан поняла, в чем дело: все это время Хейл вел себя тихо, подозрительно тихо, поскольку отлично знал, что нет такой диагностики, в которой использовалась бы цепная мутация, тем более такая, которая занимала ТРАНСТЕКСТ уже восемнадцать часов. Хейл не проронил ни слова.
Теперь он уже бежал по узкому проходу. Шаги все приближались. Беккер оказался на прямом отрезке, когда вдруг улочка начала подниматься вверх, становясь все круче и круче.
КОД ОШИБКИ 22 Сьюзан вздохнула с облегчением. Это была хорошая весть: проверка показала код ошибки, и это означало, что Следопыт исправен. Вероятно, он отключился в результате какой-то внешней аномалии, которая не должна повториться. Код ошибки 22. Она попыталась вспомнить, что это .
Живший в ее сознании герой умер, превратился в убийцу. Его руки внезапно снова потянулись к ней в отчаянном порыве. Он целовал ее щеки. - Прости меня, - умолял .
Солнце уже зашло. Над головой автоматически зажглись лампы дневного света.