Brent Cornell

    
Eukaryotic DNA is wrapped around histone proteins to form compact nucleosomes

• These histone proteins have protruding tails that determine how tightly the DNA is packaged

Modification of Histone Tails

Typically the histone tails have a positive charge and hence associate tightly with the negatively charged DNA

• Adding an acetyl group to the tail (acetylation) neutralises the charge, making DNA less tightly coiled and increasing transcription
• Adding a methyl group to the tail (methylation) maintains the positive charge, making DNA more coiled and reducing transcription

Acetylation of Nucleosomes

Types of Chromatin

When DNA is supercoiled and not accessible for transcription, it exists as condensed heterochromatin

When the DNA is loosely packed and therefore accessible to the transcription machinery, it exists as euchromatin

• Different cell types will have varying segments of DNA packaged as heterochromatin and euchromatin
• Some segments of DNA may be permanently supercoiled, while other segments may change over the life cycle of the cell

Nucleosome Packaging in Euchromatin and Heterochromatin

    
Direct methylation of DNA (as opposed to the histone tails) can also affect gene expression patterns

• Increased methylation of DNA decreases gene expression (by preventing the binding of transcription factors)
• Consequently, genes that are not transcribed tend to exhibit more DNA methylation than genes that are actively transcribed

Factors Contributing to DNA Methylation Patterns

Epigenetics

Epigenetics is the study of changes in phenotype as a result of variations in gene expression levels 

• Epigenetic analysis shows that DNA methylation patterns may change over the course of a lifetime
• It is influenced by heritability but is not genetically pre-determined (identical twins may have different DNA methylation patterns)
• Different cell types in the same organism may have markedly different DNA methylation patterns
• Environmental factors (e.g. diet, pathogen exposure, etc.) may influence the level of DNA methylation within cells

Comparative DNA Methylation Patterns in Twins of Different Ages

Comparative Methylation Patterns in Twins of Differing Health Status (Healthy vs Diseased)

Adapted from:

• Experiment 1:  Mapping Differential Methylation between MZ twins using AIMS (Fraga et al. PNAS, 2005)
• Experiment 2:  Epigenetic Regulation of Inflammatory Bowel Disease (Backdahl et al., Int J Biochem Cell Biol, 2009)