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

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

Normal cell vs Cancer cell Epigenetics ?

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)

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

Normal cell vs Cancer cell

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

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

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

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

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

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

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

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

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

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

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 ↑

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

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

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

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

Normal cell vs Cancer cell

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

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