Cancer epigenetic Flashcards
Which epigenetic changes can occur
- Histone modification (aa change in the tail - changing charge)
- Chromatin remodeling and organization
- Histone variants
- DNA methylation
- Non-coding RNA
How does Acetylation modify gene expression
Changes the interaction between histone and DNA, less binding of Histone to DNA –> more Transcription
How does Methylation modify gene expression
Binds to the backbone of DNA and affect the accessibility to gene –> less transcription
Can work as a docking station for TF in that case increase transcription
How does Chromatin remodeling modify gene expression
Chromatin remodeling is the relaxation or condensation of the DNA around the chromatin affecting the accessibility of genes
How does Histone variants modify gene expression
There are different variants of histones, which one that bind affect the activation or inactivation of genes
Hos does DNA methylation modify gene expression
DNA methylation happens on CpG islands and affect transcription of genes:
- Silencing genes by preventing binding of regulatory factors
- Affecting binding of chromatin to DNA
These can be added and removed by enzymes
How does non-coding RNA modify gene expression
Either non-coding RNA inhibit the translation of genes by bindning to mRNA or transcription of genes by blocking bindning of TF. But it can also work as docking for regulatory factors to the DNA, thereby increasing the transcription
In what way is epigenetics important in cancer
- Transcription is deregulated in cancer due to mutations in epigenetic enzymes
- Causing down regulation of TSG
- Causing activation of oncogenes
- Deregulation of genes contributes to clonal advantages promoting cancer development
- Effecting clonal evolution, changes complexity and adaptive flexibility of the cells - another level of diversity in tumor
Importance of cancer epigenetic in clinical aspects
- Epigenetic changes contribute to the heterogeneity of tumors, making them non-responsive to one type of treatment, instead different targets are needed
- Epigenetic enzymes are good targets, since these are easier to target than changing genome, although they affect gene expression in the same way.
