You Are What Your Mother Ate: The Science of Epigenetics

Transcription

1 You Are What Your Mother Ate: The Science of Epigenetics Daniel Lieber Kerry Samerotte Brian Beliveau October 6, 2010

2 Part III: Epigenetics: Past, Present, & Future

3 How did we discover epigenetics? Schneiderman et al. PLoS Genet Sep 9;6(9)

4 Eye Color in Fruit Flies (1938) Pigmentation gene: ON OFF Schneiderman et al. PLoS Genet Sep 9;6(9)

5 Eye Color in Fruit Flies (1938) OFF Variable boundary ON DNA Histone Nucleosome Pigmentation gene Schneiderman et al. PLoS Genet Sep 9;6(9)

6 Color changing corn (?!)

7 Paramutation (1956) Expect Observe X X X 100% 50% 50% 100%

8 Paramutation (1956) All have identical DNA sequences X X X Pigmentation Pigmentation Pigmentation gene gene OFF ON gene OFF J. Corum for NYTimes

9 The Case of the Calico Cat

10 What are sex chromosomes? X X Mom Dad X Y Mom Dad

11 Are two X s better than one? X X X Y Mom Dad or X X Mom Dad Mom Dad Adapted from

12 X-inactivation (1961) X O X B X O X B

13 Key Points 1. A gene s local environment is important 2. Changes to a gene s environment can be stably inherited

14 Major Open Questions Where? When? Memory? ON ON vs.???? vs. OFF OFF???? What gets passed on? J. Corum for NYTimes

15 What gets passed on in mice? Study published August 2010 Question: Does the Y chromosome pass on epigenetic information? Looked at a panel of behavioral traits Found epigenetic effects to be on par with genetic effects Study Nelson et al. Epigenomics 2010 Aug;2(4)

16 A Tale of Two Chromosomes Imprinting: When parental chromosomes are marked differently On Off Off On On Off Mom Dad Adapted from

17 Imprinting & Chromosome 15 Angelman Syndrome Prader-Willi Syndrome deletion Off Off deletion Mom Dad Mom Dad Adapted from Angelman Syndrome Gene Reviews - NCBI Bookshelf

18 Imprinting More widespread than we thought? Study published August 2010 Looked at imprinting in the mouse brain Known Imprinted genes New Study Gregg et al. Science Aug 2010;329(5992)

19 Other epigenetic effects

20 Epigenetics & Cancer Myelodysplastic Syndromes (MDS) Disease of bone marrow High risk of leukemia Delayed onset (>60 years old) 3 yrs 50 yrs Methyl group H 3 C First MDS drug to show a survival benefit Azacitidine (Vidaza) Cytosine ( C ) Fraga et al. Proc Natl Acad Sci U S A Jul 26;102(30):

21 Epigenetics & Memory?? Mouse with memory defects Exposure to lively environment Mouse with improved memory Offspring with improved memory!

22 Source NCBI Pub Med Database Tip of the Iceberg?

23 Summary Weird phenomena in model systems gave us early clues about epigenetics Scientists are actively trying to understand how epigenetic information is specified and transmitted Epigenetics can inform our design of therapeutics We still have a lot to learn about epigenetics!

24 Thank you! Questions?

25 Thank you! SITN would like to acknowledge the following organizations for their generous support: Harvard Medical School Office of Communications and External Relations Division of Medical Sciences The Harvard Graduate School of Arts and Sciences (GSAS) The Harvard Biomedical Graduate Students Organization (BGSO) The Harvard/MIT COOP Restaurant Associates - SITN is a student organization at Harvard GSAS-