SCRB 155: Epigenetic Regulation in Stem Cells and Development
Spring 2012
Description:
Cloning of Dolly the sheep suggests that all of our cells have exactly the same genes as a fertilized egg. If this is true, then
how is it that each of our cells reads out those genes differently? This course will explain the epigenetic mechanisms that
regulate the expression of genes, as well as how this developmental expression is established, maintained and how it can
be reversed during cellular reprogramming.
Instructor:
Alexander Meissner (AM)
Bauer Laboratory, Room 207
7 Divinity Avenue
alexander_meissner@harvard.edu
Assistant:
Andrea Boyle
Bauer Laboratory
7 Divinity Ave, Rm 210
Cambridge, MA 02138
phone: (617) 496-0870
andrea_boyle@harvard.edu
Teaching Fellow:
Lillian Zwemer (LZ)
merriam@fas.harvard.edu
Course time:
Tuesdays and Thursdays
11:30am-1:00pm
Location:
Biolabs 1058
Office hours:
Thursdays
1:30pm-2:30pm (or arrange any time with Andrea)
Course Grading:
2 Problem sets: 20%
Discussion: 25%
Midterm: 25%
Final: 30%
Prerequisites:
Life and Physical Sciences A or Life Sciences 1a; Life Sciences 1b; MCB 52 or MCB54 or
permission of the instructor
Lecture
Date
Topic
1
1/24
(Tu)
Lecture 1 (AM): Introduction to Epigenetics and SCRB155
Course overview; General introduction into epigenetics, epigenomics and
epigenetic mechanisms including their role in development and disease; Stem
cells and reprogramming
2
1/26
(Th)
Lecture 2 (AM/LZ): Overview of class assignments, problem sets and discussion
sections; introduction to presenting and discussing scientific papers
Paper: Okano 1999 Cell
3
1/31
(Tu)
Lecture 3 (AM): DNA Methylation-Part1
Introduction into DNA methylation, history, current understanding and genomic
distribution as well as its establishment and maintenance
4
2/2
(Th)
Paper Discussion (LZ/AM):
Review: Bird 2002 Genes & Development
Primary: Chen 2003 Molecular & Cellular Biology
Primary: Athanasiadou 2010 PLoS One
5
2/7
(Tu)
Lecture 4 (AM): DNA Methylation-Part2 /Histone Modifications-Part1
Sites of DNA methylation and mechanisms of demethylation;
Hydroxymethylation (5-hmC); Introduction to
histone modifications and the histone code
6
2/9
(Th)
Paper Discussion (LZ/AM):
Review: Branco 2012 Nature Reviews Genetics
Primary: Gu. 2011 Nature
Primary: Williams 2011 Nature
7
2/14
(Tu)
Lecture 5 (AM): Histone Modifications-Part2 (1st Problem set due)
The readers and writers; polycomb and trithorax; chromatin states
8
2/16
(Th)
Paper Discussion (LZ/AM):
Review: Prezioso 2011 FEBS
Primary: Woo 2010 Cell
Primary: Zhao 2010 Cell
9
2/21
(Tu)
Lecture 6 (AM): Histone Variants and Nuclear Architecture
Role and distribution of histone variants, higher order chromatin structure and
nuclear architecture.
10
2/23
(Th)
Midterm review session (LZ)
11
2/28
(Tu)
Lecture 7 (guest lecture John Rinn): Non-Coding RNAs
Non-coding RNAs emerged as important regulators and interactors with the
epigenetic machinery in the past years. We will provide an overview of the field
and summarize the latest advancements.
Website: http://www.rinnlab.com/
12
3/1
(Th)
Midterm
13
3/6
(Tu)
Lecture 8 (AM): Reading the Epigenome (Technologies)
Introduction to next generation sequencing technologies and their applications
for DNA methylation and chromatin mapping
14
3/8
(Th)
Tour of the Sequencing Center at the Broad Institute of MIT and Harvard
3/10 – 3/18
Spring Break
15
3/20
(Tu)
Lecture 9 (guest lecture Ben Ebert): Epigenetics in Human Disease-Part1
Examples of epigenetic diseases with a particular focus on cancer
Website: http://ebertlab.bwh.harvard.edu/
16
3/22
(Th)
Paper Discussion (LZ):
Review: Jones 2007 Cell
Primary: Berman 2011 Nature Genetics
17
3/27
(Tu)
Lecture 10 (AM): Epigenetics in Human Disease-Part2 (Environmental
Epigenetics)
Role of environmental influences on the epigenome including diet, aging and
other exposures.
18
3/29
(Th)
Paper Discussion (LZ/AM):
Review: Kouzarides 2007 Cell
Primary: Ernst 2011 Nature
19
4/3
(Tu)
Lecture 11 (AM): Epigenetic Mechanisms in Development-Part1
Role of epigenetic modifications in early development; dynamic changes during
differentiation; genomic imprinting; x-inactivation
20
4/5
(Th)
Field trip to local Epigenetics Company (TBA) (2nd Problem set due)
21
4/10
(Tu)
Lecture 12 (AM): Epigenetic Mechanisms in Development-Part2
Epigenetic mechanisms involved in adult development
22
4/12
(Th)
Lecture 13 (AM): Epigenetics and Pluripotency
Mouse and human ES cells; pluripotency and developmental plasticity
23
4/17
(Tu)
Lecture 14 (AM): Epigenetic Reprogramming
Mechanisms of cellular reprogramming including nuclear transfer and induced
pluripotent stem (iPS) cells.
24
4/19
(Th)
Paper Discussion (LZ/AM):
Review: Plath 2011 Nature Reviews Genetics
Primary: Koche 2011 Cell Stem Cell
Primary: Takahashi 2006 Cell
25
4/24
(Tu)
Finals review session
Finals (TBA)