Gene regulation
From Freepedia
Gene regulation is the general term for modulation of gene expression, the cellular control of the amount and timing of appearance of the functional product of a gene. Although a functional gene product may be an RNA or a protein, the majority of the known mechanisms of gene regulation are from protein coding genes. Any step of gene expression may be modulated, from the DNA-RNA transcription step to protein synthesis. Gene regulation gives the cell the broadest control over structure and function, and is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism. Examples of gene regulation include the induction of heat shock proteins in the fruit fly Drosophila melanogaster.
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Mechanisms for gene regulation
Chemical modification of DNA
Methylation of DNA is a common method of gene silencing. DNA is typically methylated by methyltransferase enzymes on cytosine nucleotides in a CpG dinucleotide sequence (also called "CpG islands"). Analysis of the pattern of methylation in a given region of DNA (generally a promoter) can be achieved through a method called bisulphite mapping. Methylated cytosine residues are unchanged by the treatment, whereas unmethylated ones are changed to uracil. The differences are analyzed in sequencing gels. Abnormal methylation patterns are thought to be involved in carcinogenesis.
Structural modification of DNA
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 histones 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.
Acetylation of the arms of histones is also an important process 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 acetylation 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 machinery
In order for a gene to be expressed, several things must happen. Firstly, there needs to be an initiating signal. This is achieved through the binding of some ligand 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 acetylateed, and DNA is transcribed into RNA.
Frequently, extracellular signals induce the expression of immediate early genes (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.
