Regulation of gene expression (or gene regulation) includes the processes that cells and viruses use to turn the information in genes into gene products. Although a functional gene product may be an RNA or a protein, the majority of known mechanisms regulate protein coding genes. Any step of the gene’s expression may be modulated, from DNA-RNA transcription to the post-translationalmodification of a protein.
Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. The first discovered example of a gene regulation system was the lac operon, discovered by Jacques Monod, in which protein involved in lactose metabolism are expressed by E.coli only in the presence oflactose and absence of glucose.
Furthermore, gene regulation drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms where the different types of cells may possess different gene expression profiles though they all possess the same genomesequence.
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Modification of DNA
In eukaryotes, the accessibility of large regions of DNA can depend on its chromatin structure which can be altered as a result of histone modifications which are directed by DNA methylation, ncRNA or DNA binding protein.
Chemical
Methylation of DNA is a common method of gene silencing. DNAis typically methylated by methyltransferase enzymes on cytosine nucleotides in a CpG dinucleotide sequence (also called “CpG islands” when densely clustered). Analysis of the pattern of methylation in a given region of DNA (which can be a promoter) can be achieved through a method called bisulfite mapping. Methylated cytosine residues are unchanged by the treatment, whereas unmethylated ones arechanged to uracil. The differences are analyzed by DNA sequencing or by methods developed to quantify SNPs, measuring the relative amounts of C/T at the CG dinucleotide. Abnormal methylation patterns are thought to be involved in carcinogenesis.
Structural
Transcription of DNA is dictated by its structure. In general, the density of its packing is indicative of the frequency of transcription.Octameric protein complexes called nucleosomes are responsible for the amount of supercoiling of DNA, and these complexes can be temporarily modified by processes such as phosphorylation or more permanently modified by processes such as methylation. Such modifications are considered to be responsible for more or less permanent changes in gene expression levels.
Histone acetylation is also an importantprocess in transcription. Histone acetyltransferase enzymes (HATs) such as CREB binding protein also dissociate the DNA from the histone complex, allowing transcription to proceed. Often, DNA methylation and histone deacetylation work together in gene silencing. The combination of the two seems to be a signal for DNA to be packed more densely, lowering gene expression.————————————————-
]Regulation of transcription
Regulation of transcription controls when transcription occurs and how much RNA is created. Transcription of a gene by RNA polymerase can be regulated by at least five mechanisms:
* Specificity factors 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. sigmafactors used in prokaryotic transcription).
* Repressors 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 factors These transcription factors position RNA polymerase at the start of a protein-coding sequence and then…
