1. Epigenetics of cancer
Vilja ja Mia

2. Short summary Introduction to epigenetics (in cancer)
Epigenetical alterations in cancer vs. normal cells (DNA methylation and histone modifications, full epigenomes)
Disruption of the epigenetic machinery
Using epigenomic marks in therapeutic targets: to identify cancer cell marks, tumor prognosis, chemotherapy sensitivity
Some future ideas in cancer epigenomics

3. What is epigenetics?
= Mitotically or meiotically heritable changes in gene expression that don’t involve a change in DNA sequence.
Molecular modifications in chromatin:
DNA methylation: 5’ Cytosines in CpG
Histone modifications: Histone tail (H3, H4) acetylation, phosphate groups, methylation = “Histone code”
non-coding RNA’s: miRNA, siRNA…
Chromatin remodeling: protein complexes, SWI-SNF

4. Epigenetic marks in normal and cancer cells
Dependent on cell/tissue type!
DNA methylation:
CpG islands:
transcription starting sites (UTR-areas): hypo-/hypermethylation
imprinting (X-inactivation): hypermethylation
Repetitive sequences:
Transposable elements: hypermethylation
Histone modifications:
Acetylation: HAT/HDAC- enzymes
Methylation: H3K4me3: near the transcription start sites
Phosphorylation, Ubiquitylation, Sumoylation

5. Formation of cancer cells by epigenetical changes

6. DNA methylation:

7. Histone modifications:

8. The epigenomes of cancer cells
All epigenetical modifications taken together in certain cell type (Epigenetical pattern of cell)
DNA methylation at promoter areas:
cell-cycle inhibitor p16
DNA repair genes: MLH1, BRCA1
Tumor-suppressor genes (next picture)
Methylation patterns vary among tumor types

10. The epigenomes of cancer cells
2. Histone modifications:
Often associated with DNA methylation (CpG islands)
H4: loss of monoacetylation and trimethylation

11. Disruption of the epigenetic machinery
Genes involved in epigenetic modifications are often disrupted in cancer  preliminary data available about those genes

13. The future of cancer epigenomics
Creating epigenome maps:
Using epigenomic profiles as cancer cell markers
Tumor prognosis
Predicting chemotherapy/drugs response
Re-expression of silenced genes (therapeutic use)
 Creating human epigenome!

14. References
Esteller M., Cancer epigenomics: DNA methylomes and histone modification maps, Nature Reviews, April 2007
Jirtle L.J et al., Environmental epigenetics and disease susceptibility, Nature Reviews, April 2007
Pierce, B.A.: Genetics, a conceptual approach. W.H. Freeman and Co
Illustrating how epigenetics can control physical traits, the slimmer and browner of these mice, carrying a gene called agouti, were born to mothers that ate more DNA-methylating foods.
Credit: Jirtle/Environmental Health Perspectives

15. Class activation
Let’s play hangman!!! (=hirsipuu)