Genetics, epigenetics and their application

Theme 3 :

Genetics, epigenetics and their application

Epigenetics mechanisms

Gene can be silenced or activated. If a gene is activated, il can be « read » and used as a template for transcription followed by translation. On the other hand, genes can also be silenced. There are three mechanisms or systems of gene silencing :

DNA methylation

It is a chemical process that adds a methyl (CH3) group to DNA . It is highly specific and always happens in a region in which a cytosine © is located next to a guanine (G) nucleotide that is linked by a phosphate; CpG site.

Histone modifications

Histone can be modified by acetylation (acetyl : C2H3O) and methylation. Acetylation is usually associated with active chromatin. Histone methylation can be a marker or both active and inactive regions of chromatin.

RNA- associated silencing

RNA is the form of non-coding RNAs or RNA interference or antisense transcripts.

RNA might affect gene expression by triggering histone modifications and DNA methylation.

Epigenetics and Disease

Disrupting any of the three systems that contribute to epigenetic alterations can cause abnormal activation or silencing of genes.

Epigenetics and cancer

In case of a loss of DNA methylation, the arrangement of the chromatin will be altered, consequently, the activation of the gene will be abnormally high.

In case of an overdose of methylation, the tumor suppressor genes will be silenced which will lead to the apparition of tumors.

If there is an excessive quantity of methyl groups in cancer cells, the genes that are normally active will be silenced.

Moreover, the instability of microsatellites (=repeated sequences of DNA which can be linked to many cancer) is due to hypermethylation.

Epigenetics and mental retardation

The most frequent inherited mental disease (which touches particularly men) is the fragile X syndrome. Its symptoms are severe intellectual disabilities, delayed verbal development, and “autistic-like” behavior. Its cause is the inactivation of the FMR1 gene, so the loss of its protein.

Combating diseases with epigenetic therapy

The aim of epigenetic therapy is the alter DNA methylation or histone methylation.

For DNA methylation, the silent gene can be reactivated thanks to inhibitors. They will incorporate themselves into DNA to stop DNA methylation.

For histone methylation, the acetyl groups are removed thanks to histone deacetylase inhibitors. Then, it will turn on the gene expression.

Epigenetic treatment must be used very carefully in irregular cells to be successful, otherwise, these treatments can lead to cancer.

Mutation: modification of DNA sequence.

HIV: Human Immunodeficiency Virus -> AIDS: Acquired Immune-Deficiency Syndrome

Enzymes: proteins that facilitate chemical reactions.

Vocabulary:

Pandemic: pandémie (worldwide# epidemic>in limited area) To disrupt: perturber

Strain: souche To delay: retarder

Cutting-edge: à la pointe de To counteract: contrer

Unprecedented: sans précédent

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