1. Gene Expression and Epigenetic Regulation JESSICA LAINE AND ELIZABETH MARTIN

2. The Central Dogma of Biology

3. How does the cell control these processes?

4. Research Questions in the Fry Lab  What is the relationship between prenatal arsenic exposure and changes to gene expression?  Are any of the genes that are altered in association with arsenic controlled by the epigenetic mechanism DNA methylation?

5. How were these questions investigated?  38 newborns  Arsenic exposure  DNA Methylation Profiles  RNA (Gene expression) Profiles

6. Is there is a relationship between prenatal exposure to arsenic and functional epigenetic changes to newborn DNA ?

7. Microarray analysis was used to determine which genes exhibited differential expression  The microarray works by first extracting DNA or RNA and hybridizing different pieces representing different genes to a transcript  It allows us to measure how many copies of each gene is expressed (i.e. has transcript)  This can tell us whether there is no, some or a lot of RNA transcript in the cell

8. What is a heatmap and how do you read it? Lower iAs Higher iAs ? ? ? ?

9. 334 U-tAs-associated transcripts N=38 subjects with range of arsenic exposure, cord blood (vein) isolated Multi-variable models for association between arsenic exposure-prenatal and gene expression N=224 N=110 A heatmap is a way to visualize data trends U-tAs (µg/L)

10. Conclusions  There are 334 genes that show a change in transcript profiles in association with arsenic exposure in the 38 babies in the BEAR cohort  There are gene that expression changes in both a positive and negative way: some genes expression profiles increase with increasing arsenic exposure and some gene expression profiles decrease with decreased arsenic exposure  These changes suggest that prenatal arsenic exposure does affect a baby’sgene expression profile

11. Are any of the genes that are altered in association with arsenic controlled by the epigenetic mechanism DNA methylation?

12. The traditional view of DNA methylation

13. What would you expect to find?

14. What did we see when looking at individual genes?

15. DNA Methylation Gene Methylation RNA Transcript Gene Expression

16. Where do these measurements come from?

17. What conclusions can we draw from this?  Methylation does indeed control for some genes’ gene expression, in this study we found 16 genes were controlled by gene expression  Some of these genes were related to important birth outcome including gestational age and head circumference

18. Questions?

19. What did the researchers actually find?

20. This pattern is present across the entire genome!