About this course: While the human genome sequence has transformed our understanding of human biology, it isn’t just the sequence of your DNA that matters, but also how you use it! How are some genes activated and others are silenced? How is this controlled? The answer is epigenetics. Epigenetics has been a hot topic for research over the past decade as it has become clear that aberrant epigenetic control contributes to disease (particularly to cancer). Epigenetic alterations are heritable through cell division, and in some instances are able to behave similarly to mutations in terms of their stability. Importantly, unlike genetic mutations, epigenetic modifications are reversible and therefore have the potential to be manipulated therapeutically. It has also become clear in recent years that epigenetic modifications are sensitive to the environment (for example diet), which has sparked a large amount of public debate and research. This course will give an introduction to the fundamentals of epigenetic control. We will examine epigenetic phenomena that are manifestations of epigenetic control in several organisms, with a focus on mammals. We will examine the interplay between epigenetic control and the environment and finally the role of aberrant epigenetic control in disease. All necessary information will be covered in the lectures, and recommended and required readings will be provided. There are no additional required texts for this course. For those interested, additional information can be obtained in the following textbook. Epigenetics. Allis, Jenuwein, Reinberg and Caparros. Cold Spring Harbour Laboratory Press. ISBN-13: 978-0879697242 | Edition: 1
Who is this class for: Some background in biology, and more specifically genetics is recommended. If you don't have a genetics background, or want to brush up on genetics before you start, you might like to consider taking one of these MOOCs before our course starts (copy and paste the URLs) ❖ Introduction to Genetics and Evolution: https://www.coursera.org/learn/genetics-evolution ❖ Genes and The Human Condition (From Behaviour to Biotechnology): https://www.coursera.org/learn/genes ❖ Genomic Medicine gets Personal: https://www.edx.org/course/genomic-medicine-gets-personal-georgetownx-medx202-02x
Created by: The University of Melbourne
Taught by: Dr. Marnie Blewitt, Head, Molecular Medicine Laboratory
Walter and Eliza Hall Institute of Medical Research
| Commitment | 7 weeks of study, 6-8 hours/week |
| Language | English |
| How To Pass | Pass all graded assignments to complete the course. |
| User Ratings |
Syllabus
WEEK 1
Week 1 - Introduction to Epigenetic Control
An introduction to and definition of epigenetic control of gene expression, and its importance in normal development. We will learn what chromatin is, and how its composition and packaging can alter gene expression. We’ll also discuss the best-characterised epigenetic modification, DNA methylation, and how it is not only implicated in regulating gene expression, but also in maintaining genome stability.
7 videos, 5 readings
- Reading: Course syllabus
- Reading: Teaching team
- Reading: Start of course survey
- Reading: Assessment and grading policy
- Video: 1.1 Introduction to the concepts of epigenetic control
- Video: 1.2 Mitotic heritability of epigenetic marks
- Video: 1.3 Chromatin and the nucleosome
- Video: 1.4 Chromatin compaction - heterochromatin versus euchromatin
- Video: 1.5 DNA methylation at CpG islands
- Video: 1.6 DNA methylation at intergenic regions and repetitive elements
- Reading: Week 1 and 2 resources
Graded: Week 1 quiz - contributes 8% towards your final grade
WEEK 2
Week 2 - Epigenetic Modifications and Organisation of the Nucleus
We’ll discuss the molecular mechanisms for regulating gene expression in some detail, from how the DNA is packaged at a local level, right up to how the chromatin is positioned within the nucleus. We’ll learn about the chromatin modifications implicated in gene silencing and activation, the role of non-coding RNA, and higher order chromatin structures. This week will provide you with a good understanding of the basic mechanisms that will help you understand the processes we discuss throughout the rest of the course.
9 videos, 1 reading
- Video: 2.2 Histone acetylation and histone methylation
- Video: 2.3 Chromatin remodelling
- Video: 2.4 Histone variants
- Video: 2.5 Noncoding RNAs - microRNAs
- Video: 2.6 Noncoding RNAs - piRNAs
- Video: 2.7 Noncoding RNAs - long noncoding RNAs introduction
- Video: 2.8 Long noncoding RNAs Xist and HOTAIR
- Video: 2.9 3D organisation of the nucleus and summary of epigenetic marks
- Reading: Week 1 and 2 resources
Graded: Week 2 quiz - contributes 8% towards your final grade
WEEK 3
Week 3 - Dosage Compensation
X chromosome inactivation is a really well-characterised epigenetic process that is now used as a model system to study epigenetic processes that are relevant more broadly. This is because it uses many epigenetic mechanisms, at many levels, to achieve really stable silencing of a whole chromosome. We’ll learn about this process and how it occurs in a mouse in great detail, which will greatly add to the mechanistic understanding gained in week two. We will then briefly discuss alternate mechanisms for dosage compensation that occur in other organisms.
12 videos, 1 reading
- Video: 3.2 Timing of random and imprinted X chromosome inactivation
- Video: 3.3 Stages of X inactivation - counting and control of Xist expression
- Video: 3.4 Control of Xist expression by pluripotency factors
- Video: 3.5 Stages of X inactivation - choice of which X to inactivate
- Video: 3.6 Stages of X inactivation - initiation and spreading of silencing
- Video: 3.7 Stages of X inactivation - establishment of silencing
- Video: 3.8 Stages of X inactivation - maintenance of silencing e.g. Dnmt1
- Video: 3.9 Stages of X inactivation - maintenance of silencing e.g. Smchd1
- Video: 3.10 X chromosome inactivation summary
- Video: 3.11 Dosage compensation in flies and worms, compared with mammals
- Video: 3.12 Lessons from the fly - position effect variegation and screening for epigenetic modifiers
- Reading: Week 3 resources (including required readings)
Graded: Week 3 quiz - contributes 12% towards your final grade
WEEK 4
Week 4 - Genomic Imprinting and Epigenetic Reprogramming
We’ll learn about the two important periods during development for the erasure and resetting of the epigenome. There are two well-characterised features that are treated differently during epigenetic reprogramming; imprinted genes and repeats. We’ll learn about mechanisms for genomic imprinting, and study three examples in more depth.
6 videos, 1 reading
- Video: 4.2 Epigenetic reprogramming of imprinted genes and repetitive elements
- Video: 4.3 Location of imprinted genes in the genome and bisulfite sequencing
- Video: 4.4 Kcnq1 and H19/Igf2 ICR mechanisms of action and Beckwith Weidemann syndrome
- Video: 4.5 Snrpn ICR mechanism, Prader Willi and Angelman syndromes
- Video: 4.6 Summary of epigenetic reprogramming and imprinting
- Reading: Week 4 resources (including required reading)
Graded: Week 4 quiz - contributes 12% towards your final grade
WEEK 5
Week 5 - The Influence of the Environment on Epigenetic Control
We start to look at some of the big areas of interest in human epigenetics, including environmental influence on the epigenome, reprogramming of somatic cells back to stem cells, cloning, and potential transgenerational epigenetic inheritance. We’ll discuss what is known to happen to the epigenome during these process, and look at some seminal case studies.
6 videos, 1 reading
- Video: 5.2 Disrupted epigenetic reprogramming in somatic cell reprogramming and cloning
- Video: 5.3 Introduction of transgenerational epigenetic inheritance, effects of the environment and sensitive periods in epigenetic control
- Video: 5.4 The Dutch Famine human epidemiological studies and the Developmental Origins of Adult Health and Disease
- Video: 5.5 Human epidemiological studies on the Overkalix cohort, grandparental effects and possibility of transgenerational epigenetic inheritance in humans
- Video: 5.6 Extension lecture: Interview with Dr Andrew Keniry
- Reading: Week 5 resources (including required readings)
Graded: Week 5 quiz - contributes 12% towards your final grade
WEEK 6
Week 6 - Mechanisms of Environmental Influence on Epigenetic Control and Transgenerational Epigenetic Inheritance Through the Gametes
A look at the mechanisms underlying some of the observations we discussed in week 5, through the study of model organisms. We’ll learn about metastable epialleles, which have allowed the study of transgenerational epigenetics in mice, and provided some evidence for transgenerational epigenetics in mammals.
8 videos, 1 reading
- Video: 6.2 Transgenerational epigenetic inheritance via the gametes
- Video: 6.3 The Agouti viable yellow allele in mice
- Video: 6.4 Environmental effects on the Agouti viable yellow allele
- Video: 6.5 The Axin fused allele in mice and metastable epialleles
- Video: 6.6 Potential mechanisms of transgenerational epigenetic inheritance: incomplete epigenetic reprogramming
- Video: 6.7 Paramutation in plants and paramutation-like effects in mice
- Video: 6.8 Constitutional epimutation in humans - not transgenerational epigenetic inheritance
- Reading: Week 6 resources (including required readings)
Graded: Week 6 quiz - contributes 12% towards your final grade
WEEK 7
Week 7 - Cancer Epigenetics
This week we’ll bring together much of what we’ve learned in previous weeks of the course, to understand how the epigenome is affected, and can also affect, cancer development and progression. We’ll then go on to discuss the potential therapeutic benefits that can come from using epigenetic biomarkers, and targeting epigenetic modifiers in cancer.
11 videos, 3 readings
- Video: 7.2 Hypermethylation of CpG islands in cancer
- Video: 7.3 Hypermethylation of sets of CpG islands in cancer
- Video: 7.4 Hypomethylation genome-wide in cancer
- Video: 7.5 Altered histone modifications in cancer
- Video: 7.6 Long range epigenetic alterations in cancer and alterations to nuclear architecture
- Video: 7.7 Altered expression on piRNAs and long noncoding RNAs in cancer
- Video: 7.8 Mutations in epigenetic modifiers in cancer
- Video: 7.9 Drugs that target the epigenetic machinery as chemotherapeutics
- Video: 7.10 Extension lecture: Aging - Part 1
- Video: 7.11 Extension lecture: Aging - Part 2
- Reading: Week 7 resources (including required readings)
- Reading: Academic integrity
- Reading: End of course survey
Graded: Epigenetics and Cancer - contributes 36% towards your final grade
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Ratings and Reviews
Excellent course
This was an excellent course. All the material was well presented and the explanation of the sometimes complex subject matter was clear and understandable. Thank you for an great learning experience.
I enjoyed and learnt a lot about epigenetics by taking part in this great course. The content is clear and very well explained. The Professor is outstanding! Thanks
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HK
This course is well taught and some important concepts are repeated over and over again during the course so the concept lingers in the brain as if it was there already.