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Encyclopedia > Gene regulation

Gene regulation is the general term for cellular control of protein synthesis at the DNA-RNA transcription step. Since this is the root of the central dogma of biology, gene regulation gives the cell the broadest control over structure and function. The level of broad control, however, comes at the expense of timing; since the effects of any change in gene regulation are far downstream, gene regulation is often used for processes which have relatively long-term effects, in contrast to signal transduction which is how the cell handles events quickly (though often it results in gene regulation). Examples of gene regulation include heat shock proteins generated by the fruit fly Drosophila melanogaster. In biochemistry, protein synthesis refers to the creation of a macromolecule from amino acids. ... Transcription is the process through which a DNA sequence is enzymatically copied by an RNA polymerase to produce a complementary RNA. In the case of protein-encoding DNA, transcription is the beginning of the process that ultimately leads to the translation of the genetic code (via the mRNA intermediate) into... The central dogma of molecular biology (sometimes Cricks central dogma after Francis Crick who coined the term and discovered some of the principles) states that the flow of genetic information is DNA to RNA to protein. With a few notable exceptions, all biological cells conform to this rule. ... In biology, signal transduction is any process by which a cell converts one kind of signal or stimulus into another. ... A heat shock protein (HSP) is a group of proteins which increase their expression when the cells which contain them are exposed to elevated temperatures. ... Binomial name Drosophila melanogaster Meigen, 1830 Drosophila melanogaster (Black-bellied Dew-lover) a dipteran (two-winged) insect, is the species of fruit fly that is commonly used in genetic experiments; it is among the most important model organisms. ...

Contents


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. In biology, histones are the chief proteins of chromatin. ... Phosphorylation is the addition of a phosphate (PO4) group to a protein or a small molecule. ... Methylation refers to the replacement of a hydrogen atom (H) with a methyl group (CH3), regardless of the substrate. ...


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. In molecular biology, a transcription factor is a protein that binds DNA at a specific promoter or enhancer region or site, where it regulates transcription. ... Phosphorylation is the addition of a phosphate (PO4) group to a protein or a small molecule. ... Proteolysis is the directed degradation (digestion) of proteins by cellular enzymes called proteases or by intramolecular digestion. ...


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.


  Results from FactBites:
 
ScienceDaily: BRCA2 (1532 words)
BRCA2 is a human gene that is involved in the repair of chromosomal damage and belongs to a class of genes known as tumor suppressor genes.
BRCA2 -- BRCA2 is a human gene that is involved in the repair of chromosomal damage and belongs to a class of genes known as tumor suppressor genes.
Gene therapy -- Gene therapy is the insertion of genes into an individual's cells and tissues to treat a disease, and hereditary diseases in particular.
January 15, 2003 Scientists identify hundreds of worm genes that regulate fat storage (988 words)
The identified genes were very diverse and included both the expected genes involved in fat and cholesterol metabolism as well as new candidates, some that are expected to function in the central nervous system.
The challenge now is for scientists to unravel these regulatory pathways and prioritize the relevant genes in animal models, such as the worm and the mouse.
Some of the newly identified worm fat regulatory genes are predicted to function in its nervous system, as are the human counterparts to these worm genes.
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