1. Epigenetic modulators, modifiers and mediators
in normal cell and cancer cell
Lab of Chromatin Biology
Kang Yujin

2. Contents Epigenetics Features of normal cell and cancer cell
Normal cell vs Cancer cell
Contents
Epigenetics
Features of normal cell and cancer cell
Classification in the epigenetics of cancer
- Epigenetic modifiers
- Epigenetic mediators
- Epigenetic modulators
Summary

3. Normal cell vs Cancer cell
Epigenetics ?

4. Features of normal cells
Normal cell vs Cancer cell
Features of normal cells
- Reproduce themselves only when and where they are needed
- Stick together in the right place in the body
- Self destruct if they are damaged or too old
- Become specialised (mature)

5. Features of cancer cells - Don't stop growing and dividing
Normal cell vs Cancer cell
Features of cancer cells
- Don't stop growing and dividing
- Don't repair themselves or die
- Don't specialise
- Look different

6. Normal cell vs Cancer cell

7. Normal cell vs Cancer cell
Ageing or aging is the process of becoming older. It represents the accumulation of changes in a person over time

8. Normal cell vs Cancer cell
Molecular Cell 54, June 5, 2014

9. Normal cell vs Cancer cell
Three classification in the epigenetics of cancer
1. Epigenetic modifiers
: A gene that modifies DNA methylation or chromatin structure in cancer
2. Epigenetic mediators
: A gene regulated by an epigenetic modifier in cancer that increases pluripotency or survival
3. Epigenetic modulators
: A gene that activates or represses the epigenetic machinery in cancer

10. Three classification in the epigenetics of cancer
Normal cell vs Cancer cell
Three classification in the epigenetics of cancer
1. Epigenetic modifiers
- Chromatin remodelling
- DNA methylation
- Histone acetylation
- Histone methylation

11. Normal cell vs Cancer cell
NATURE REVIEWS | GENETICS VOLUME 17 | MAY 2016 |

12. Typical hallmark of cancer
Normal cell vs Cancer cell
VOLUME 17 | NUMBER 3 | MARCH 2011 nature medicine
DNA methylation pattern disruption ↓
Typical hallmark of cancer

13. Normal cell vs Cancer cell
nature medicine VOLUME 17 | NUMBER 3 | MARCH 2011

14. Normal cell vs Cancer cell
Molecular Cell 54, June 5, 2014

15. Three classification in the epigenetics of cancer
Normal cell vs Cancer cell
Three classification in the epigenetics of cancer
2. Epigenetic mediators
- ex) OCT4, NANOG, SOX2, KLF4

16. Normal cell vs Cancer cell
NATURE REVIEWS | GENETICS VOLUME 17 | MAY 2016 |
LOCKs : Large organized chromatin K9 modifications
LADs : lamina-associated domains

17. Normal cell vs Cancer cell
NATURE REVIEWS | GENETICS VOLUME 17 | MAY 2016 |
H3K9 demethylase (LSD1) recruitment ↓
H3K9me2 and H3K9me3 ↓
Chromatin remodelling complex recruitment ↓
Gene activity ↑

18. Three classification in the epigenetics of cancer
Normal cell vs Cancer cell
Three classification in the epigenetics of cancer
3. Epigenetic modulators
- tumour suppressor protein p53
- Adonomatous polyposis coli (APC) tumour suppressor gene

19. Normal cell vs Cancer cell
tumour suppressor protein p53 mutation ↓
Histone modifying enzyme MLL1, MLL2(mixed-lineage leukemia) induce
H3K4me3 increases
cancer

20. Normal cell vs Cancer cell
tumour suppressor protein p53 mutation ↓
Physical interaction with the SWI/SNF chromatin remodelling complex
Promoter remodelling
cancer

21. Normal cell vs Cancer cell
Adonomatous polyposis coli (APC) tumour suppressor gene mutation ↓
DNA demethylase upregulation
Hypomethylated cell fate
cancer

22. Normal cell vs Cancer cell

23. References Normal cell vs Cancer cell
Panagiotis Ntziachristos, et al. Emerging concepts of epigenetic dysregulation in hematological
malignancies, Nature immunology, 2016
Andrew P. Feinberg, et al. Epigenetic modulators, modifiers and mediators in cancer aetiology and
progression, Nature, 2016
Hariharan Easwaran, et al. Cancer epigenetics; tumor heterogeneity, plasticity of stem-like states,
and drug resistance, Mol Cell, 2014
Manuel Rodriguez-Paredes, Manel Esteller. Cancer epigenetics reaches mainstream oncology,
Nature medicine, 2011
Pater A. Jones and Stephen B. Baylin. The fundamental role of epigenetic events in cancer, Nature, 2002

24. THANK YOU