Factors affecting methylation: early life & beyond

Question 1

Genetic: Genomic Imprinting

Answer 1

• Silencing of one copy of each gene, depending on sex of parent from which it was inherited
• Only happens in 1% of genome, usually the sex of the parent is irrelevent
• Placental genes are paternally inherited, hence maternal-fetal conflict
• Tortoiseshell cats are always female… ‘mosaicism’ in colour caused by different genes being switched on or off (‘X-Sliencing’: Turning off one copy of the x chromosome in each cell to prevent producing double quantities. Whether it is the maternal or paternal x that is switched off varies from cell-cell.)

Question 2

Environment: Diet triggers

Answer 2

Example:
• Royal jelly (royalactin) is associated with methylation changes in countless genes, and leads to difference in development of queens and workers!
- These differences are epigenetic rather than genetic, all changes happen because of royal jelly. (Workers have increased methylation)

Question 3

Environment: Nutrition

Answer 3

• Affect of famine in early life: influences methylation of genes involved with insulin-like growth factors
(imprinting gene from father – want to extract as much resource from mother as possible)
• Paternal diet effects on daughters – influences methylation of sperm, and therefore offspring: In this study, High-fat-diet fathers led to daughters with increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity.
o Shea-Fang et al, Nature 2010

Question 4

Hormonal: Stress

Answer 4

• Maternal depression leads to increased methylation in foetal chord blood
• Partner violence during pregnancy associated with increased blood methylation of juveniles
• In rats, even living with stressed individuals can cause methylation changes in parts of the brain
• Abuse and neglect leads to increased methylation of parts of brain

Question 5

Maternal interaction

Answer 5

• Level of maternal care affects offspring cognition and responses to stress
• Cross-fostering confirms causality
- Dec. stress caused by reductions in methylation in promoter region of corticoid receptors
- Deal with stress better, as they can regulate cortisol better
- Decreased methylation of oestrogen receptor – so those offspring are more likely to lick their own offspring
- Increased offspring attentiveness

Question 6

During zygote development

Answer 6

IVF and Hormone therapies can influence DNA methylation patterns of imprinted genes, that can cause diseases

Question 7

During foetal development

Answer 7

Exposure to bisphenols (BPA) commonly used in baby bottles, inside of food containers and water piping, is an endocrine disrupter.
Causes changes to methylation patterns in brains of mice, rats and humans.
Generally this arises pre-natally, but also following birth, affecting brain function.

Question 8

During adult life

Answer 8

• Manipulation of testosterone in adult rats influences methylation of vasopressin receptors, influencing water retention and blood pressure….probably humans too
• Stress: a terrible thing with multiple consequences, see other card

Question 9

Key point

Answer 9

Evidence that DNA methylation influenced by multiple factors at multiple levels throughout development & life in general. What happens to you in your life CAN affect your offspring