C9041 Structure and function of eukaryotic chromosomes

Faculty of Science
Spring 2017
Extent and Intensity
2/0/0. 2 credit(s) (fasci plus compl plus > 4). Type of Completion: zk (examination).
Teacher(s)
prof. RNDr. Jiří Fajkus, CSc. (lecturer)
doc. Mgr. Miloslava Fojtová, CSc. (lecturer)
doc. RNDr. Martin Falk, Ph.D. (lecturer)
Guaranteed by
prof. RNDr. Jiří Fajkus, CSc.
National Centre for Biomolecular Research – Faculty of Science
Contact Person: prof. RNDr. Jiří Fajkus, CSc.
Supplier department: National Centre for Biomolecular Research – Faculty of Science
Timetable
Mon 20. 2. to Mon 22. 5. Fri 8:00–9:50 B11/235
Prerequisites
basic knowledge of biochemistry and molecular biology
Course Enrolment Limitations
The course is also offered to the students of the fields other than those the course is directly associated with.
fields of study / plans the course is directly associated with
Course objectives
Main objectives: Students will gain a detailed knowledge on chromatin structure, as the carrier of genetic and epigenetic information
In the end of the course, the students will be able to understand current knowledge on molecular basis of epigenetic processes
Student will gain a detailed overview of the structure and function of telomeres, centromeres and replication origins
Syllabus
  • Lectures are focused on description of chromosomes and their dynamic changes during basic processes of metabolism of genetic material - replication, transcription and recombination. Besides relations to gene functioning, possible and described functions of so called noncoding sequences forming the DNA components of essential chromosome elements - centromeres and telomeres will be discussed. SYLLABUS 1. Chromosome as a functional unit of genome. Types of chromosomes (prokaryotic or eukaryotic, mitochondrial, chloroplast, circular and linear. Characterisation of individual types based on nucleoprotein composition and DNA size. Examples. 2. Linear eukaryotic chromosomes as a typical example of structural units of nuclear eukaryotic gene. Structural levels of chromosome - an overview. Metaphase and interphase chromosome. Chromatin. 3. DNA folding into chromosomes (total 10000 times). Compactisation of DNA on formation of nucleoprotein complexes with histones. Nucleosome, chromatosome, core particle. Binding of H1 histone. Translational and rotational position of nucleosome on DNA. 4. Nucleosomes at replication and transcription. Mechanisms of regulation of gene expression by modification of nucleosome structure. Examples. Experimental approaches for determination of nucleosome structure. Computer predictions. Non-nucleosomal DNA. 5. Further compactisation of nucleosome array - model structures of 30 nm fibre - solenoid and zig-zag. Experimental findings. Role of conformation of internucleosomal linker ana histone H1 binding. Association with nonhistone proteins, namely HMGA, HMGB and HMGN. 6. Epigenetic modifications of genetic information. Modification of histones and methylation of DNA, histone variants and their function, remodelling of chromatin structure. Examples of processes - X-chromosome inactivation, promoter activation/silencing. 7. Higher-order chromatin structure - loops (cca 50 kbp) anchored to nuclear matrix. Nuclear matrix, nuclear skeleton, nuclear scaffold - differences and similarities. Binding of chromatin fibre to these structures. Experimentally determined types of binding: permanent and transient, covalent and non-covalent. 7. RNA interference mechanism and its role in heterochromatinisation and gene silencing. Examples of natural processes. Application of siRNA strategy in functional studies. 8. Higher-order chromatin structure - model and experimentally observed structures. Practical approaches for mapping MARs. Role of topoisomerase II in nucleoprotein complexes of nuclear matrix. Replication and transcription in "factories" anchored to nuclear skeleton. Regulation of gene expression at the level of chromatin loops. Rosette structures and chromosome "minibands"(2 Mb) - last levels of chromosome compactisation. Chromosome territories. Heterochromatin and euchromatin from the point of view of different structural levels. Isochores. 9. Specialised chromosome structures - centromere and telomere. Fuctions determined and suggested. Light microscopy view and nucleoprotein composition - generally. 10. Detailed telomere structure - telomeric DNAs at different organisms, associated proteins, telomerase - specialised reverse transcriptase possessing its own template RNA. Telomerase as a target of anticancer therapy. Telomerase-independent mechanisms of telomere maintenance. 11. Recombination as an example of process of metabolism of genetic information. Types of recombination processes and their molecular mechanisms. Using recombination as a tool in genetics.Role of recombination in genome integrity. Role of recombination proteins at telomeres. 12. Centromere - example of "non-coding" repetitive sequences, which (in interaction with specific proteins) code for functionally indispensable chromosome domain. Establishment of centromeric heterochromatin. 13. Functional chromosome = centromere, telomeres and replication origins? Methods of mapping replication origins. Attempts to construct mammalian artificial chromosome (MAC) and perspective use. 14. Chromatin restructuring in spermatogenesis. How the extreme compactisation is achieved (Proteins change, DNA remains). What happens with chromatin after fertilisation of egg cell. 15. Structure of the cell nucleus and chromatin in association with principle life processes, namely DNA repair: new views on induction and repair of double-strand DNA breaks - spatiotemporal aspects, dsDNA breaks as a claymore in origin and treatment of tumours.
Literature
  • Bryan M. Turner: Chromatin and gene regulation. Molecular mechanisms in epigenetics. Blackwell Science Ltd. ISBN 0-865-42743-7
  • T.A. Brown: GENOMES. Bios Scientific Publishers Ltd. 1999,Oxford.
  • C.R. Calladine, H.R. Drew: Understanding DNA.Second edition. Academic Press N.Y. 1997
  • FAJKUS, Jiří and Ulrike ZENTGRAF. Structure and Maintenance of Chromosome Ends in Plants. In Telomerases, Telomeres and Cancer. Georgetown, New York: Landes Bioscience, Kluwer Academic, 2002, p. 314-331. Molecular Biology Intelligence Unit 22. ISBN 0-306-47437-9. info
Teaching methods
Lectures; analysis of examples of research problems concerning topics of the lectures
Assessment methods
Written test and oral exam. Written test preceeds oral exam. To pass the oral exam, >50% of correct answers in the test are required. Both parts of the exam may be performed in English if preferred by a student.
Language of instruction
Czech
Follow-Up Courses
Further comments (probably available only in Czech)
The course is taught annually.
Listed among pre-requisites of other courses
The course is also listed under the following terms Spring 2013, Spring 2014, Spring 2015, Spring 2016, spring 2018, Spring 2019, Spring 2020, Spring 2021, Spring 2022, Spring 2023, Spring 2024, Spring 2025.
  • Enrolment Statistics (Spring 2017, recent)
  • Permalink: https://is.muni.cz/course/sci/spring2017/C9041