Genetics and Molecular Biology

LUCIA PIACENTINI

Epigenetics is the study of heritable changes in gene expression that do not involve changes in the DNA sequence.The course aims to discuss and explore the molecular mechanisms that regulate epigenetic phenomena (chromatin remodeling, histone modification and histone code, heterochromatic proteins, DNA methylation, RNA interference) and the cellular processes that exploit this kind of regualtion (genomic and chromosomal imprinting, facultative heterochromatin, chromosome elimination, position effect of variegation and paramutation).
In addition this course will allow students to learn modern approaches to study the chromatin modifications. We will examine most interesting non-canonical genetic events that involve epigenetic mechanisms. In nature, in fact, exist many variations of basic biological processes, such as meiosis and mitosis, and chromosomal structures, such as telomeres and centromeres. The aim is to demonstrate that the study of non-canonical genetic systems allows to obtain meaningful information about their evolutionary significance and the corresponding canonical processes. A further goal is to illustrate the biology of transposons and their role in gene expression and genomic organization.

The term Epigenetics includes all phenomena that induce a differential and heritable gene expression without modifications in the DNA sequence.
The Epigenetics course aims to discuss and explore the molecular mechanisms that regulate epigenetic phenomena (chromatin remodeling, heterochromatic proteins, histone modifications and the histone code, DNA methylation, RNA interference) and the cellular processes that rely on this type of regulation (genomic and chromosomal imprinting, facultative heterochromatinization, chromosomal elimination, position-effect variegation, paramutation).

The course will also cover the most advanced techniques for analyzing chromatin modifications and will discuss the most recent discoveries in the field of epigenetics. In addition, some of the most interesting non-canonical genetic phenomena involving epigenetic mechanisms in a broad sense will be presented. In nature, there is a wide range of variants of fundamental biological processes such as meiosis and mitosis, as well as of chromosomal structures such as telomeres and centromeres.

The goal is to demonstrate that studying non-canonical genetic systems provides meaningful insights into their evolutionary relevance and into the corresponding canonical processes. The biology of transposons and their role in gene expression and genome organization will also be addressed.

Students who successfully pass the exam will be able to know and understand (acquired knowledge):
• The structural and functional organization of the eukaryotic genome
• The molecular bases of epigenetic regulation
• The cellular phenomena and processes that rely on epigenetic regulation
• The methods and technologies used to study epigenetic chromatin modifications
• Non-canonical genetic systems involving epigenetic mechanisms

Students will also be able to (acquired skills):
• Evaluate the impact of epigenetic regulation on the modulation of genome functions
• Interpret the complex molecular networks that control epigenetic regulation
• Apply their knowledge of chromatin modification analysis techniques to design laboratory experiments, selecting the most appropriate methods for different experimental problems
• Understand and critically interpret experimental results in epigenetics and epigenomics
• Deepen their understanding of the topics and develop their own discussion on specific subjects covered in the course.

Students should have a good knowledge of Genetics, basic Molecular and Cell Biology, and the main techniques of Genetic Engineering.

Mitosis and meiosis: canonical mechanisms and their variants
- meiotic drive
- inverted meiosis
- chromosome and chromatin elimination
Eukaryotic Chromosome Oragnization
- Centromeres and telomeres
- monocentric and holocentric chromosomes
Transposable Elements and Genome Evolution
Symbiosis
- Host-Microbiome Interactions
- the hologenome theory of evolution
Epigenetics in social insects
Molecular mechanisms of epigenetics
- DNA Methylation
- Histone modifications and Histone code
- Chromatin remodeling complexes
- RNA interference and non-coding RNAs
- Three-Dimensional Architecture of Genomes and Chromosome Conformation Capture
Epigenetic phenomena
- Facultative Heterochromatin
- Position Effect of Variegation (PEV)
- Paramutation and Cosuppression in plants
- Genetic and Genomic imprinting
- Transgenerational epigenetic effects.
Methods of DNA methylation analysis
- Cobra Technology (Combined bisulfite Restriction Analysis)
- Real time MSP and methyLight
- Pyrosequencing and massARRAY
- Methylation-Specific Digital Karyotiping (MSDK)
- Methylated-CpG Island Recovery Assay (MIRA)
- Methylated DNA Immunoprecipitation (MeDIP)
Epigenetics and Human Diseases
- Cancer Epigenetics
- Epigenetics and neurodegenerative diseases: Rett syndrome (RS)
- Epigenetics in Immune Disorders
- Imprinting Disorders in Humans
- Epigenetic Therapy

Genetica_Pimpinelli_Ambrosiana. Caso di studio 8_Epigenetics
Reviews and articles selected from scientific literature

Handbook of Epigenetics. The New Molecular and Medical Genetics. Edited by: Trygve O. Tollefsbol
Gene Regulation and Epigenetics. How Science Works. Carsten Carlberg. Published by
Springer Nature Switzerland, January 2024. ISBN: 978-3-03-168730-3
Allison B. Herman, Dimitrios Tsitsipatis, Myriam Gorospe, Integrated lncRNA function upon genomic and epigenomic regulation, Molecular Cell,Volume 82, Issue 12,2022,Pages 2252-2266,
https://doi.org/10.1016/j.molcel.2022.05.027.
Transgenerational Epigenetics. 2nd Edition, Volume 13 - May 21, 2019. Academic Press. Editor: Trygve O. Tollefsbol. ISBN: 9780128163634

The course includes theoretical lectures (5CFU) and practical sessions (1CFU)

Attendance is not mandatory

The oral exam consists of an interview with the instructor to verify the achievement of the objectives in terms of knowledge and skills acquired, as well as communication skills, language proficiency, clarity of exposition, and critical ability to solve genetic problems.
The time spent on the oral exam is about 20/30 minutes.

The questions cover the entire course program