Epigenetic Control of Gene Expression

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Epigenetic Control of Gene Expression

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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 t…

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When you enroll for courses through Coursera you get to choose for a paid plan or for a free plan

  • Free plan: No certicification and/or audit only. You will have access to all course materials except graded items.
  • Paid plan: Commit to earning a Certificate—it's a trusted, shareable way to showcase your new skills.

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 4.8 stars Average User Rating 4.8See what learners said Coursework

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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.

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 expand


  1. Video: Course overview
  2. Reading: Course syllabus
  3. Reading: Teaching team
  4. Reading: Start of course survey
  5. Reading: Assessment and grading policy
  6. Video: 1.1 Introduction to the concepts of epigenetic control
  7. Video: 1.2 Mitotic heritability of epigenetic marks
  8. Video: 1.3 Chromatin and the nucleosome
  9. Video: 1.4 Chromatin compaction - heterochromatin versus euchromatin
  10. Video: 1.5 DNA methylation at CpG islands
  11. Video: 1.6 DNA methylation at intergenic regions and repetitive elements
  12. 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 expand


  1. Video: 2.1 Introduction to histone tail modifications
  2. Video: 2.2 Histone acetylation and histone methylation
  3. Video: 2.3 Chromatin remodelling
  4. Video: 2.4 Histone variants
  5. Video: 2.5 Noncoding RNAs - microRNAs
  6. Video: 2.6 Noncoding RNAs - piRNAs
  7. Video: 2.7 Noncoding RNAs - long noncoding RNAs introduction
  8. Video: 2.8 Long noncoding RNAs Xist and HOTAIR
  9. Video: 2.9 3D organisation of the nucleus and summary of epigenetic marks
  10. 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 expand


  1. Video: 3.1 History and background of X chromosome inactivation
  2. Video: 3.2 Timing of random and imprinted X chromosome inactivation
  3. Video: 3.3 Stages of X inactivation - counting and control of Xist expression
  4. Video: 3.4 Control of Xist expression by pluripotency factors
  5. Video: 3.5 Stages of X inactivation - choice of which X to inactivate
  6. Video: 3.6 Stages of X inactivation - initiation and spreading of silencing
  7. Video: 3.7 Stages of X inactivation - establishment of silencing
  8. Video: 3.8 Stages of X inactivation - maintenance of silencing e.g. Dnmt1
  9. Video: 3.9 Stages of X inactivation - maintenance of silencing e.g. Smchd1
  10. Video: 3.10 X chromosome inactivation summary
  11. Video: 3.11 Dosage compensation in flies and worms, compared with mammals
  12. Video: 3.12 Lessons from the fly - position effect variegation and screening for epigenetic modifiers
  13. 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 expand


  1. Video: 4.1 Introduction to epigenetic reprogramming of the maternal and paternal genomes
  2. Video: 4.2 Epigenetic reprogramming of imprinted genes and repetitive elements
  3. Video: 4.3 Location of imprinted genes in the genome and bisulfite sequencing
  4. Video: 4.4 Kcnq1 and H19/Igf2 ICR mechanisms of action and Beckwith Weidemann syndrome
  5. Video: 4.5 Snrpn ICR mechanism, Prader Willi and Angelman syndromes
  6. Video: 4.6 Summary of epigenetic reprogramming and imprinting
  7. 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 expand


  1. Video: 5.1 Disrupted epigenetic reprogramming in assisted reproductive technologies
  2. Video: 5.2 Disrupted epigenetic reprogramming in somatic cell reprogramming and cloning
  3. Video: 5.3 Introduction of transgenerational epigenetic inheritance, effects of the environment and sensitive periods in epigenetic control
  4. Video: 5.4 The Dutch Famine human epidemiological studies and the Developmental Origins of Adult Health and Disease
  5. Video: 5.5 Human epidemiological studies on the Overkalix cohort, grandparental effects and possibility of transgenerational epigenetic inheritance in humans
  6. Video: 5.6 Extension lecture: Interview with Dr Andrew Keniry
  7. 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 expand


  1. Video: 6.1 Mouse and rat studies on paternal effects of chemical exposure, effects of maternal behaviour on epigenetic makeup
  2. Video: 6.2 Transgenerational epigenetic inheritance via the gametes
  3. Video: 6.3 The Agouti viable yellow allele in mice
  4. Video: 6.4 Environmental effects on the Agouti viable yellow allele
  5. Video: 6.5 The Axin fused allele in mice and metastable epialleles
  6. Video: 6.6 Potential mechanisms of transgenerational epigenetic inheritance: incomplete epigenetic reprogramming
  7. Video: 6.7 Paramutation in plants and paramutation-like effects in mice
  8. Video: 6.8 Constitutional epimutation in humans - not transgenerational epigenetic inheritance
  9. 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 expand


  1. Video: 7.1 Overview of cancer epigenetics
  2. Video: 7.2 Hypermethylation of CpG islands in cancer
  3. Video: 7.3 Hypermethylation of sets of CpG islands in cancer
  4. Video: 7.4 Hypomethylation genome-wide in cancer
  5. Video: 7.5 Altered histone modifications in cancer
  6. Video: 7.6 Long range epigenetic alterations in cancer and alterations to nuclear architecture
  7. Video: 7.7 Altered expression on piRNAs and long noncoding RNAs in cancer
  8. Video: 7.8 Mutations in epigenetic modifiers in cancer
  9. Video: 7.9 Drugs that target the epigenetic machinery as chemotherapeutics
  10. Video: 7.10 Extension lecture: Aging - Part 1
  11. Video: 7.11 Extension lecture: Aging - Part 2
  12. Reading: Week 7 resources (including required readings)
  13. Reading: Academic integrity
  14. Reading: End of course survey

Graded: Epigenetics and Cancer - contributes 36% towards your final grade
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