1. EPIGENETICS #1
BIOT 412
Fall 2013

2. IMPRINTING
GENOME has 2 copies of each gene – one from mother, one from father
IMPRINTING - For some genes, only the copy from the mother ever gets switched on, and for others, only the copy from the father.
IGF2 only made by father’s genes
EPIGENOME is responsible
ABNORMAL IMPRINTING
Beckwith-Wiedmann syndrome, a disorder associated with body overgrowth and increased risk of cancer
Prader-Willi and Angelman syndromes, which are disorders associated with obesity and mental retardation.

5. EPIGENETIC PATHWAYS WHY IMPORTANT
Individuals have single genome but multiple epigenomes
Different in different cells and tissues
May change over lifetime
Involved in many types of disease
Identical twins become different with age

6. EPIGENETICS Cancer Aging  DNA methylation 
Hypomethylation (20-60% less) chromosome instability + oncogene activation
Hypermethylation  tumor suppressor genes silenced
Aging  DNA methylation 
Environmental factors: heavy metals, pesticide, folate and methionine deficiencies, smoking, cocaine
Type-2 diabetes, obesity, infertility, cardiovascular, mental disorders, neurodevelopmental disorders

7. EPIGENETIC PATHWAYS Four types DNA methylation Histone modification
Nucleosome remodeling
Non-coding RNA-mediated pathways
Intertwine to regulate expression of genes

9. TYPE 1: DNA Methylation CpG and CpG islands in linear DNA chain
Cytosine in CpG islands is methylated at 5th C
Methylation involved in regulating cell differentiation and function
Too much or too little
Alters cell function
Results in disease

10. TYPE 2: Histone Modification
Globular proteins; 4 main types but there are variants
Histones exist as octamer
Pairs of histone H2A, H2B, H3 and H4
One/~147 bp of genomic DNA = nucleosome
DNA + histone octamer = nucleosome = structural unit of chromatin

11. Histone Modification Above process = chromatin modification
NH2 tails of histones post-translationally modified
Acetylated (acetyltransferases - HATs, deacetylases – HDACs)
Methylated (methytransferases, demethylases)
Phosphorylated (Kinases)
Ubiquinated
Above process = chromatin modification
Provides recruitment signals for nonhistone proteins (e.g., transcription factors)
Relaxes chromatin by disrupting contacts between nucleosomes and interactions between histone tails and genomic DNA

13. certain molecules are added to or removed from DNA, making it harder or easier for the DNA to be read and translated, and thus used to make proteins essential for cells to function

15. WATCH “A TAKE OF TWO MICE”