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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%

ont commencé une nouvelle carrière après avoir terminé ce cours

38%

ont bénéficié d'un avantage concret dans leur carrières grâce à ce cours

11%

a obtenu une augmentation de salaire ou une promotion

100 % en ligne

Commencez dès maintenant et apprenez aux horaires qui vous conviennent.

Dates limites flexibles

Réinitialisez les dates limites selon votre disponibilité.

Approx. 30 heures pour terminer

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

Anglais

Sous-titres : Anglais, Espagnol

Compétences que vous acquerrez

CancerMolecular BiologyCancer EpigeneticsDna Methylation

Learner Career Outcomes

33%

ont commencé une nouvelle carrière après avoir terminé ce cours

38%

ont bénéficié d'un avantage concret dans leur carrières grâce à ce cours

11%

a obtenu une augmentation de salaire ou une promotion

100 % en ligne

Commencez dès maintenant et apprenez aux horaires qui vous conviennent.

Dates limites flexibles

Réinitialisez les dates limites selon votre disponibilité.

Approx. 30 heures pour terminer

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

Anglais

Sous-titres : Anglais, Espagnol

Programme du cours : ce que vous apprendrez dans ce cours

Semaine

1

2 heures pour terminer

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 vidéos (Total 65 min), 5 lectures, 1 quiz

7 vidéos

Course overview1 min

1.1 Introduction to the concepts of epigenetic control10 min

1.2 Mitotic heritability of epigenetic marks10 min

1.3 Chromatin and the nucleosome6 min

1.4 Chromatin compaction - heterochromatin versus euchromatin9 min

1.5 DNA methylation at CpG islands11 min

1.6 DNA methylation at intergenic regions and repetitive elements15 min

5 lectures

Course syllabus10 min

Teaching team10 min

Start of course survey10 min

Assessment and grading policy10 min

Week 1 and 2 resources10 min

1 exercice pour s'entraîner

Week 1 quiz - contributes 8% towards your final grade20 min

Semaine

2

2 heures pour terminer

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 vidéos (Total 90 min), 1 lecture, 1 quiz

9 vidéos

2.1 Introduction to histone tail modifications4 min

2.2 Histone acetylation and histone methylation12 min

2.3 Chromatin remodelling12 min

2.4 Histone variants8 min

2.5 Noncoding RNAs - microRNAs6 min

2.6 Noncoding RNAs - piRNAs9 min

2.7 Noncoding RNAs - long noncoding RNAs introduction10 min

2.8 Long noncoding RNAs Xist and HOTAIR7 min

2.9 3D organisation of the nucleus and summary of epigenetic marks17 min

1 lecture

Week 1 and 2 resources10 min

1 exercice pour s'entraîner

Week 2 quiz - contributes 8% towards your final grade20 min

Semaine

3

3 heures pour terminer

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 vidéos (Total 113 min), 1 lecture, 1 quiz

12 vidéos

3.1 History and background of X chromosome inactivation13 min

3.2 Timing of random and imprinted X chromosome inactivation8 min

3.3 Stages of X inactivation - counting and control of Xist expression13 min

3.4 Control of Xist expression by pluripotency factors6 min

3.5 Stages of X inactivation - choice of which X to inactivate9 min

3.6 Stages of X inactivation - initiation and spreading of silencing11 min

3.7 Stages of X inactivation - establishment of silencing6 min

3.8 Stages of X inactivation - maintenance of silencing e.g. Dnmt18 min

3.9 Stages of X inactivation - maintenance of silencing e.g. Smchd18 min

3.10 X chromosome inactivation summary10 min

3.11 Dosage compensation in flies and worms, compared with mammals8 min

3.12 Lessons from the fly - position effect variegation and screening for epigenetic modifiers10 min

1 lecture

Week 3 resources (including required readings)10 min

1 exercice pour s'entraîner

Week 3 quiz - contributes 12% towards your final grade30 min

Semaine

4

2 heures pour terminer

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 vidéos (Total 68 min), 1 lecture, 1 quiz

6 vidéos

4.1 Introduction to epigenetic reprogramming of the maternal and paternal genomes9 min

4.2 Epigenetic reprogramming of imprinted genes and repetitive elements11 min

4.3 Location of imprinted genes in the genome and bisulfite sequencing10 min

4.4 Kcnq1 and H19/Igf2 ICR mechanisms of action and Beckwith Weidemann syndrome17 min

4.5 Snrpn ICR mechanism, Prader Willi and Angelman syndromes13 min

4.6 Summary of epigenetic reprogramming and imprinting6 min

1 lecture

Week 4 resources (including required reading)10 min

1 exercice pour s'entraîner

Week 4 quiz - contributes 12% towards your final grade30 min

Semaine

5

2 heures pour terminer

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 vidéos (Total 90 min), 1 lecture, 1 quiz

6 vidéos

5.1 Disrupted epigenetic reprogramming in assisted reproductive technologies15 min

5.2 Disrupted epigenetic reprogramming in somatic cell reprogramming and cloning15 min

5.3 Introduction of transgenerational epigenetic inheritance, effects of the environment and sensitive periods in epigenetic control9 min

5.4 The Dutch Famine human epidemiological studies and the Developmental Origins of Adult Health and Disease9 min

5.5 Human epidemiological studies on the Overkalix cohort, grandparental effects and possibility of transgenerational epigenetic inheritance in humans12 min

5.6 Extension lecture: Interview with Dr Andrew Keniry26 min

1 lecture

Week 5 resources (including required readings)10 min

1 exercice pour s'entraîner

Week 5 quiz - contributes 12% towards your final grade18 min

Semaine

6

2 heures pour terminer

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 vidéos (Total 102 min), 1 lecture, 1 quiz

8 vidéos

6.1 Mouse and rat studies on paternal effects of chemical exposure, effects of maternal behaviour on epigenetic makeup14 min

6.2 Transgenerational epigenetic inheritance via the gametes10 min

6.3 The Agouti viable yellow allele in mice15 min

6.4 Environmental effects on the Agouti viable yellow allele11 min

6.5 The Axin fused allele in mice and metastable epialleles14 min

6.6 Potential mechanisms of transgenerational epigenetic inheritance: incomplete epigenetic reprogramming9 min

6.7 Paramutation in plants and paramutation-like effects in mice13 min

6.8 Constitutional epimutation in humans - not transgenerational epigenetic inheritance12 min

1 lecture

Week 6 resources (including required readings)10 min

1 exercice pour s'entraîner

Week 6 quiz - contributes 12% towards your final grade20 min

Semaine

7

5 heures pour terminer

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 vidéos (Total 144 min), 3 lectures, 1 quiz

11 vidéos

7.1 Overview of cancer epigenetics7 min

7.2 Hypermethylation of CpG islands in cancer16 min

7.3 Hypermethylation of sets of CpG islands in cancer11 min

7.4 Hypomethylation genome-wide in cancer12 min

7.5 Altered histone modifications in cancer11 min

7.6 Long range epigenetic alterations in cancer and alterations to nuclear architecture10 min

7.7 Altered expression on piRNAs and long noncoding RNAs in cancer9 min

7.8 Mutations in epigenetic modifiers in cancer9 min

7.9 Drugs that target the epigenetic machinery as chemotherapeutics17 min

7.10 Extension lecture: Aging - Part 114 min

7.11 Extension lecture: Aging - Part 223 min

3 lectures

Week 7 resources (including required readings)10 min

Academic integrity10 min

End of course survey10 min

Enseignant

Dr. Marnie Blewitt

Head, Molecular Medicine Laboratory

Walter and Eliza Hall Institute of Medical Research

Foire Aux Questions

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Le contrôle épigénétique de l'expression des gènes