Stages of gene expression
nesstar said:
I'm a bit confused about methylation/demethylation and acetylation/deacetylation. I'm just going to outline my shaky understanding, so if someone could clarify, correct or confirm that would be very helpful!
Unpacking of DNA involves DNA demethylation and histone acetylation
Methylation and deacetylation block the DNA from expression.
There are a number of stages at which gene expression can be controlled in eucaryotic cells. While transcription is an important stage, it is not the only one.
STAGE ONE - UNPACKING - DNA is bundled or wound around protiens called histones to form structures called nucleosomes in the nucleus of cells. This helps to store a large amount of DNA in a small space. But it also regulates gene expression. Genes that are permenently switched off my be packed very tightly or highly condensed. It is like storing winter clothes in mothballs in clothes bags. The addition of acetyl groups (-COCH3) has the opposited effect. Because the acetyl groups bind to the histone (protien) instead of the DNA, the histones change shape and bind less tightly to the DNA. This allows transcription of the DNA to occur more easily.
STAGE TWO - TRANSCRIPTION: This is a very common control point for gene expression. It is the point at which DNA is transcribed by RNA polymerase. In eucaryotic cells, each gene has its own promoter. It has control elements (pieces of non-coding DNA) that bind to transcription factors and the promotor to initiate the activity of RNA polymerase.
STAGE THREE - REGULATION OF m-RNA: The average length of a gene along a DNA molecule is about 8000 bases. Therefore the m-RNA produced from the DNA template is also 8000 bases long. It has been found that only about 1200 nucleotides (therefore bases) are required to produce an average protien of 400 amino acids long. So there must be a large amount of DNA and consequently m-RNA that is not coded into protien. The surprising finding was made that these non-coding nucleotides are interspersed among the coding nucleotides. The non-coding parts are called intervening sequences or introns and since the coding pars are expressed they are called exons. The introns must be cut out before the m-RNA leaves the nucleus. Then the exons are stuck together or spliced. One way of changing the expression of genes is to treat different segments as introns or exons in different cases so producing different m-RNA molecules from the same RNA transcript. Some genes are regulated in this way. Regulatory protiens control the splicing and may be different in different cells.
The ends of the transcribed RNA are 'capped' with protective nucleotides that prevent breakdown by hydrolytic enzymes and also help the m_RNA to attatch to the ribosome. Gene regulation may also take place by shortening the life of the m-RNA so that protien synthesis is stopped. This is done by the removal of the protective caps, after which the m-RNA is degraded.
In some cases the movement of m-RNA out of the nucleus is a stage at which the regulation of gene expression may occur. Some protiens facilitate this movement and the introns themselves play a role in either retaining the RNA in the nucleus or allowing it to move to the cytomplasm.
STAGE FOUR - CONTROL OF TRANSLATION: Translation of the m-RNA can be blocked if specific protiens bind to the m-RNA so that it connot attatch to the ribosomes.
STAGE FIVE - PROTEIN PROCESSING AND DEGRADATION: Gene expression can still take place even when the polypeptide is synthesised. Frequently, polypeptides must be processed in order to produce functional protiens. This may involve folding, cleavage (cutting of parts) or the addition of non-protien sections such as carbohydrates or lipids or other activating parts. The processed protein may then need to be transported to its site of action. Regulation may occur if any of these steps is inhibited. Some proteins have short used-by dates and must be degraded. This degradation acts as a control for the expression of the gene that produces the protein. Huge 'garbage bins' called proteasomes collect them and the proteasome enzymes destory the protiens. Defective and damaged protiens are also removed in this way.
Sometimes this has serious consequences. The disease cystic fibrosis is caused by a mutation in a gene that produces a protein involved in the transport of chloride ions across membranes. This results in a defective protein, which is degraded by proteasomes so there is no chloride ion channel protein.
There you go...hope that helps
