Epigenetic Control of Gene Expression

The University of Melbourne

About this Course

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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

Learner Career Outcomes

33%

started a new career after completing these courses

38%

got a tangible career benefit from this course

11%

got a pay increase or promotion

Shareable Certificate

Earn a Certificate upon completion

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Start instantly and learn at your own schedule.

Flexible deadlines

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Approx. 30 hours to complete

Suggested: 7 weeks of study, 6-8 hours/week...

English

Subtitles: English, Spanish

Skills you will gain

CancerMolecular BiologyCancer EpigeneticsDna Methylation

Learner Career Outcomes

33%

started a new career after completing these courses

38%

got a tangible career benefit from this course

11%

got a pay increase or promotion

Shareable Certificate

Earn a Certificate upon completion

100% online

Start instantly and learn at your own schedule.

Flexible deadlines

Reset deadlines in accordance to your schedule.

Approx. 30 hours to complete

Suggested: 7 weeks of study, 6-8 hours/week...

English

Subtitles: English, Spanish

Syllabus - What you will learn from this course

Week

Week 1

2 hours to complete

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.

2 hours to complete

7 videos (Total 65 min), 5 readings, 1 quiz

7 videos

Course overview1m

1.1 Introduction to the concepts of epigenetic control10m

1.2 Mitotic heritability of epigenetic marks10m

1.3 Chromatin and the nucleosome6m

1.4 Chromatin compaction - heterochromatin versus euchromatin9m

1.5 DNA methylation at CpG islands11m

1.6 DNA methylation at intergenic regions and repetitive elements15m

5 readings

Course syllabus10m

Teaching team10m

Start of course survey10m

Assessment and grading policy10m

Week 1 and 2 resources10m

1 practice exercise

Week 1 quiz - contributes 8% towards your final grade20m

Week

Week 2

2 hours to complete

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.

2 hours to complete

9 videos (Total 90 min), 1 reading, 1 quiz

9 videos

2.1 Introduction to histone tail modifications4m

2.2 Histone acetylation and histone methylation12m

2.3 Chromatin remodelling12m

2.4 Histone variants8m

2.5 Noncoding RNAs - microRNAs6m

2.6 Noncoding RNAs - piRNAs9m

2.7 Noncoding RNAs - long noncoding RNAs introduction10m

2.8 Long noncoding RNAs Xist and HOTAIR7m

2.9 3D organisation of the nucleus and summary of epigenetic marks17m

1 reading

Week 1 and 2 resources10m

1 practice exercise

Week 2 quiz - contributes 8% towards your final grade20m

Week

Week 3

3 hours to complete

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.

3 hours to complete

12 videos (Total 113 min), 1 reading, 1 quiz

12 videos

3.1 History and background of X chromosome inactivation13m

3.2 Timing of random and imprinted X chromosome inactivation8m

3.3 Stages of X inactivation - counting and control of Xist expression13m

3.4 Control of Xist expression by pluripotency factors6m

3.5 Stages of X inactivation - choice of which X to inactivate9m

3.6 Stages of X inactivation - initiation and spreading of silencing11m

3.7 Stages of X inactivation - establishment of silencing6m

3.8 Stages of X inactivation - maintenance of silencing e.g. Dnmt18m

3.9 Stages of X inactivation - maintenance of silencing e.g. Smchd18m

3.10 X chromosome inactivation summary10m

3.11 Dosage compensation in flies and worms, compared with mammals8m

3.12 Lessons from the fly - position effect variegation and screening for epigenetic modifiers10m

1 reading

Week 3 resources (including required readings)10m

1 practice exercise

Week 3 quiz - contributes 12% towards your final grade30m

Week

Week 4

2 hours to complete

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.

2 hours to complete

6 videos (Total 68 min), 1 reading, 1 quiz

6 videos

4.1 Introduction to epigenetic reprogramming of the maternal and paternal genomes9m

4.2 Epigenetic reprogramming of imprinted genes and repetitive elements11m

4.3 Location of imprinted genes in the genome and bisulfite sequencing10m

4.4 Kcnq1 and H19/Igf2 ICR mechanisms of action and Beckwith Weidemann syndrome17m

4.5 Snrpn ICR mechanism, Prader Willi and Angelman syndromes13m

4.6 Summary of epigenetic reprogramming and imprinting6m

1 reading

Week 4 resources (including required reading)10m

1 practice exercise

Week 4 quiz - contributes 12% towards your final grade30m

Week

Week 5

2 hours to complete

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.

2 hours to complete

6 videos (Total 90 min), 1 reading, 1 quiz

6 videos

5.1 Disrupted epigenetic reprogramming in assisted reproductive technologies15m

5.2 Disrupted epigenetic reprogramming in somatic cell reprogramming and cloning15m

5.3 Introduction of transgenerational epigenetic inheritance, effects of the environment and sensitive periods in epigenetic control9m

5.4 The Dutch Famine human epidemiological studies and the Developmental Origins of Adult Health and Disease9m

5.5 Human epidemiological studies on the Overkalix cohort, grandparental effects and possibility of transgenerational epigenetic inheritance in humans12m

5.6 Extension lecture: Interview with Dr Andrew Keniry26m

1 reading

Week 5 resources (including required readings)10m

1 practice exercise

Week 5 quiz - contributes 12% towards your final grade18m

Week

Week 6

2 hours to complete

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.

2 hours to complete

8 videos (Total 102 min), 1 reading, 1 quiz

8 videos

6.1 Mouse and rat studies on paternal effects of chemical exposure, effects of maternal behaviour on epigenetic makeup14m

6.2 Transgenerational epigenetic inheritance via the gametes10m

6.3 The Agouti viable yellow allele in mice15m

6.4 Environmental effects on the Agouti viable yellow allele11m

6.5 The Axin fused allele in mice and metastable epialleles14m

6.6 Potential mechanisms of transgenerational epigenetic inheritance: incomplete epigenetic reprogramming9m

6.7 Paramutation in plants and paramutation-like effects in mice13m

6.8 Constitutional epimutation in humans - not transgenerational epigenetic inheritance12m

1 reading

Week 6 resources (including required readings)10m

1 practice exercise

Week 6 quiz - contributes 12% towards your final grade20m

Week

Week 7

5 hours to complete

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.

5 hours to complete

11 videos (Total 144 min), 3 readings, 1 quiz

11 videos

7.1 Overview of cancer epigenetics7m

7.2 Hypermethylation of CpG islands in cancer16m

7.3 Hypermethylation of sets of CpG islands in cancer11m

7.4 Hypomethylation genome-wide in cancer12m

7.5 Altered histone modifications in cancer11m

7.6 Long range epigenetic alterations in cancer and alterations to nuclear architecture10m

7.7 Altered expression on piRNAs and long noncoding RNAs in cancer9m

7.8 Mutations in epigenetic modifiers in cancer9m

7.9 Drugs that target the epigenetic machinery as chemotherapeutics17m

7.10 Extension lecture: Aging - Part 114m

7.11 Extension lecture: Aging - Part 223m

3 readings

Week 7 resources (including required readings)10m

Academic integrity10m

End of course survey10m

Instructor

Dr. Marnie Blewitt

Head, Molecular Medicine Laboratory

Walter and Eliza Hall Institute of Medical Research

About The University of Melbourne

The University of Melbourne is an internationally recognised research intensive University with a strong tradition of excellence in teaching, research, and community engagement. Established in 1853, it is Australia's second oldest University....

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Epigenetic Control of Gene Expression