What is Epigenetics?
pattern of inheritance in which a gene or chromosome is modified temporarily. changes the gene expression, function or regulate the DNA, Protein or RNA molecules WITHOUT changing the primary sequence.
Are the changes Stable or Dynamic?
they can be both but they are not permanent. the resulting gene expression is not permanent.
where do these changes occur in?
can be during oogenesis, spermatogenesis or early stages of embryonic development. Can be removed too!
What are the examples of Epigenetic Regulations?
- Twins - Genome are identical
- embryogenesis in female mammals
- Epigenetic inactive X chromosome that female inherit from parents.
what is the reason behind chromosome inactivation?
nobody knows its still not yet understood but according to research it says mammals cell only allow X chromosome to stay active and deactivate the rest
what happens to inactive ones?
they form barr body
what is genome imprinting?
- another form of epigenetic inheritance where the gene is depended on parent sex.
- non mandelian inheritance
- permanent in somatic cells but marking of allele can be changed from generation.
can offspring express both maternally/paternally?
no only one
either maternally or paternally inherited allele
(monoallelic Expression)
what is DNA Methylation?
Common Epigenetic Modification
a chemical marking process that is important for genomic imprinting.
Imprinting + DNA Methylation Process
A methyl group CH3 is added onto the cytosine based in DNA in the regions required for gene regulation and expression. Results in Inhibition of gene expression aka silencing gene :)
where does Imprinting+DNA Methylation takes place?
either in sperm or oocyte but never in both.
what are classical genetics controlled by?
Promoters
Enhancers
Protein binding sites (present in DNA sequence)
what is an example of this regulation ? (classic genetics, genetic regulation)
control of expression of a cellular oncogene in cancer.
explain what happens in control of expression of cellular oncogene?
normally in cells this gene is not expressed but in cancer cells it causes a mutation which changes the DNA sequence. allows the oncogene to be expressed and starts developing cancer.
can epigenetic mechanism regulate other cellular processes too?
yes
what are the difference between genetic and epigenetic regulation
Epigenetics dont change the DNA sequence while genetic mechanism changes the primary DNA sequence or Mutations to this sequence.
epigenetics are the changes after the regulation of genetic mechanisms.
What are the models of Epigenetic Research?
- Budding Yeast Saccharomyces Cerevisiae
- Protozoan Tetrahymena Therophila
- Drosophila Melanogaster - classic model
- Arabidopsis Thaliana - plant model with considerable epigenetic mech as mammals
- Mice - similar to human - used for embryology.
epigenetic biological applications
- controls the expression of embryonic development genes
- X-chromosome inactivation
- Development of stem cells
- Differentiation of somatic cells
- Making of differentiated cells from adult stem cells and specific cell type
- Erasure + reestablishment of DNA methylation.
Cancer related applications
- age related DNA methylation biomarkers are linked with diseases.
- Many DNA methylation biomarkers have been found to be linked with Cancer
- many tumour suppressor genes show hypermethylation and in other cancers it shows hypomethylation.
how exactly are epigenetic mechanisms applied in types of Cancer ?
- Silencing of tumour supressor
2 Activation of oncogenes - histone modifications
what class of drugs used in Cancer Treatment?
Some examples -
1. DNA Methyl-transferase inhibitors
2. Histone De-acetylase inhibitors
how does the treatment work tho?
Epigenetic markers linked with specific diseases.
new tools to diagnose and assess the severity of disease
therapeutic epigenetics
Chemotherapy Drugs
- Azacitidine (Vidaza)
- Decitabine (Dacogen)
- Vorinostat (Zolinza)
- Romidepsin (Istodax)
What is the mode of action of Azacitidine?
make genes fight cancerous cells when given at VERY low doses. also found effective for lung cancer.
