lec 17

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University of Toronto Scarborough
Biological Sciences
Patrick Mc Gowan

BIOC14 Lecture 17 SlidesREVIEW D Maternal care can have a huge affect on the number of different processes and behaviours D Prof talked about his researchtried to look at the regulation of gene expression through epigenetic mechanism as a funciton of early maternal care in rat They used a microaarrray approach where they immunoprecipitated either the component sof chromatin or DNA methylation What they did was precipitated the DNA with an antibody that recognized DNA methylation So you have a fraction of sample with an enriched population of DNA methlyation and then you compare that sample with the same individual with their standard DNA with both methylated and unmethylated fractions You hybridize both You can see where the areas are enriched and the pop has both methylated and unmethylated DNA Individuals with low maternal or high maternal care mothers you can see where they show enriched methylation You have a canonical gene which shows where the regulatory elements are on the gene You can plot the differences between the two groups in DNA methylation and histone acetalation and RNA expression and you can see the correpondance between these 3 things D DNA methylation differences occurs in the promoter and in the exons of the gene into the 3UTR And all of these areas may be important in determing the ultimate gene expression of a particular gene Having a mom with nurture the babies are less anxious Most of the differences occured in the exons of the genes rather than the promoter regionsunlike the findings from earlier studies All of these regions can play a role The direciton of the effect is that when genes are trascbrined there are more methylation in the exons and less in promoter When genes are transcribed they are open chromatin The marker that they used was the acetylation Chromatin was open in the exons of the genes that were more expressed The graph zeroes in on the candidate genes They are members of the protocadherin gene familes This is a discovery made based on being able to look across a wide range of genome It turns out that the protocadherin genes were most highly regulated epigenetically This becomes a candidate gene modulated by early maternal care This is how you discover new genes that can be new candidate genes Now that you hypothesis based on the effectson protocadherin genes that it may be involved in neuroplasticity Protocadherins are cellcell adhesion molecules and are highly involved in the brain in regulation interconnection between neurons however this is speculationsits for future research in the area D In the human brain samples there were also wide ranges differences in epigenetics signals associated with early life experiences in humans not just rats also humans Then they tried to link the ranges in epigenetics gene expression through early life experiences to the phenotype However the phenotype affects the next generation as well So the transgenerational effects are through behaviour and through germline transmission changes in sperm or eggLECTURE 17 y Cross talk between body and the brainexamples HPAchanges in stress signalling y And from the body to the brainimmune signallingy Cortisol is everywhere in the blood and it has a lot of effects in the body as welleffects in digestive system shutting down motility in the gut and digestion effects on energy expenditure mobilizing energy from lipidsfat cells in chronic conditions and it has direct effects on the immune system as well y Stress is related to anxiety and depression but also physical conditions like hypertension coronary heart disease and ulcers y Glucocorticoid levels are higher in cases of chronic generalized anxiety disorder and depression y There are physical conditions that are associated with stressCytokine hypothesis
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