What do epigenetics do for our health?

Methylation at promoters usually results in gene expression Enhanced DNA methylation and loss of demethylation are common in cancer repression (such as tumour suppressor genes, p16, p53, BRCA1) Hypermethylation at gene body may lead to activation of oncogenes (such as DLX1, POU3F3) Active state DNA methylation is associated with drug resistance Condensed state Non-coding RNAs function through RNA-RNA, RNA-DNA, RNA- protein interaction Epigenetic regulations in cancer Cell proliferation, cell cycle control, apoptosis,metas -tasis, invasion, DNA damage, senescence TETs, HATs, HDMs HDACs are usually responsible for gene silencing and transcription repression of various genes, especially tumour suppressor genes Gene transcriptional regulation as K, / histonetail S Histone acetylation at gene promoters, enhancers, and gene body promotes gene transcription, especially oncogenes Histone methylation Repressive state Oncohistones are frequently mutated histones that are associ- -ated with tumourigenesis and cancer type specific. Transcriptionally accessible state (for example, H3K27M in —>—é"v§ <— DNMTs, HDACs, HMTs Chromatin remodeling Non-coding RNAs include tumour-promoting and tumour- suppressive two types pediatric gliomas, H3K36M in sarcoma, H3K4M in MLL) Different histone methylation sites determine gene activation (H3K9, H3K27, H4K20 ) or repression Most histone methylation enzymes are substrate-specific proteins @ DNA methylation Histone methylation - Histone acetylation (H3K4, H3K36, H3K79)