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10. Beskrive kort hvordan genekspression kan reguleres på flere niveauer: transkription, splicning, mRNA stabilitet, translation

• Transcription level: general transcription factors, specific transcription factors, promoters, enhancers, methylation of the DNA, acetylation of the histones, accessibility to the major groove.

Promoters are DNA sequences that are localised prior to the gene of interest. They have consensus sequences, and the more a promoter resembles the consensus sequence, the stronger promoter it is.

General transcription factors are proteins that bind to promoters in eukaryotes and make the initiation complex on which RNA polymerase binds and the RNA transcription begins.  

In prokaryotes, the σ-subunit of RNA polymerase binds to the promoter.

Enhancers are DNA-sequences that are located upstream, downstream or in the middle of the gene to be transcribed. They can be located as 1000 bp away from the gene. They bind the specific transcription factors and by binding them, the local structure of the chromatin changes – the promoter region and the genes itself become more available for binding transcription factors and RNA polymerase. Bounded by specific transkription factors.

Acetylation of DNA – the negatively charged DNA is packed by positively charged histone proteins. By acetylation of the positive amino acids of the histones, the bond between the DNA and the histones becomes looser and more transcription factors can bind.

Deacetylation of DNA has the opposite effect. The bond between the DNA and the histones becomes stronger and it is more difficult to get DNA in a looser form.

Methylation of DNA – a methylated DNA binds proteins that hide the promoter and enhancer sequences ad prevent the transcription factors from binding to the DNA, so transcription is low. Methylation of DNA also correlates with the deacetylation of DNA.

Transcription factors bind to the major groove of DNA, so it can be a good idea to make the groove more accessible.

• Splicing – the process in which introns are removed from the primary RNA transcript. In eukaryotic RNA, a process called alternative splicing exists. Thanks to this process, different genes can be expressed from the same pre-mRNA, forming distinct proteins for specific tissues. 30% of all human mRNAs are alternatively spliced.

• mRNA stability – the mRNA is made more stable by capping and polyadenylation. mRNA in eukaryotes has to leave the nucleus.  The more stable the mRNA is, more ribosomes have the possibility to translate it and more proteins are created. mRNA also has to be protected from the exo- and endonucleases present in the cytoplasm. A typical example of the stability of mRNA is the iron binding element.
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• Translation – the most efficient way to control translation is in the initiation stages. It can fx. include reversible phosphorilation of en elongation factor, which blocks transcription.
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