MF9225-A molecular approach to genetic and epigenetic gene regulation; from basic research to the clinic.
NOTE: The different research papers listed below will be presented in detail by the course participants. Thus, you are expected to have some knowledge on the topic of each paper while you are expected to have in-depth knowledge only on the paper that you will present (2 and 2 students will work together on the presentation of one research paper and on the first day of the course, much time will be allocated to this work). The home exam will be to write a “News and Views” article on the research paper you present (one example for the home exam is indicated below). Review papers are included to provide some background information in order to prepare the student for the research papers.
Pensum (“curriculum”):
Review: OH, the Places You'll Go! Hydroxylation, Gene Expression, and Cancer. Ploumakis A, Coleman ML. Mol Cell. 2015 Jun 4;58(5):729-41
Review: Repairing DNA-methylation damage. Sedgwick B. Nat Rev Mol Cell Biol. 2004 Feb;5(2):148-57
DNA
Review: Genomic imprinting: parental influence on the genome. Reik W, Walter J. Nat Rev Genet. 2001 Jan;2(1):21-32
Review: Epigenetic reprogramming in mammalian development. Reik W, Dean W, Walter J. Science. 2001 Aug 10;293(5532):1089-93
-Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y. Science. 2011 Sep 2;333(6047):1300-3
-Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. He YF, Li BZ, …. He C, Xu GL. Science. 2011 Sep 2;333(6047):1303-7
-Genome-wide profiling of 5-formylcytosine reveals its roles in epigenetic priming. Song CX, Szulwach KE, …. Jin P, He C. Cell. 2013 Apr 25;153(3):678-91
-Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA. Pfaffeneder T, Spada F, … H, Sch?r P, Müller M, Carell T. Nat Chem Biol. 2014 Jul;10(7):574-81
Example for home exam; News and Views; DNA metabolism: bases of DNA repair and regulation. Robertson AB, Dahl JA, Klungland A. Nat Chem Biol. 2014 Jul;10(7):487-8.
Four DNA methylation biomarkers in biliary brush samples accurately identify the presence of cholangiocarcinoma. Andresen K, Boberg KM …. Lothe RA, Lind GE.
Hepatology. 2015 May;61(5):1651-9
RNA
-Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos. Huynh KD, Lee JT. Nature. 2003 Dec 18;426(6968):857-62
-Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH. Science. 2006 Jan 20;311(5759):395-8
Review: N6-methyladenosine modification in mRNA: machinery, function and implications for health and diseases. Maity A, Das B. FEBS J. 2016 May;283(9):1607-30
-N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C. Nat Chem Biol. 2011 Oct 16;7(12):885-7
-Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Cell. 2012 Jun 22;149(7):1635-46
-A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation. Ke S, Alemu E, …. Darnell JE, Darnell RB Genes Dev. 2015 Oct 1; 29(19): 2037–2053
-Stem cells. m6A mRNA methylation facilitates resolution of na?ve pluripotency toward differentiation. Geula S, Moshitch-Moshkovitz S, …., Rechavi G, Hanna JH. Science. 2015 Feb 27;347(6225):1002-6
Protein/Histone
Review: Chromatin modifications and their function. Kouzarides T. Cell. 2007 Feb 23;128(4):693-705
-Histone demethylation by a family of JmjC domain-containing proteins. Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y. Nature. 2006 Feb 16;439(7078):811-6
-Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. Cell. 2004 Dec 29;119(7):941-53
-MLL2 is required in oocytes for bulk histone 3 lysine 4 trimethylation and transcriptional silencing. Andreu-Vieyra CV, Chen R, Agno JE, Glaser S, Anastassiadis K, Stewart AF, Matzuk MM. PLoS Biol. 2010 Aug 17;8(8)
-The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Iwase S, Lan F…. Roberts TM, Shi Y. Cell. 2007 Mar 23;128(6):1077-88
-Broad histone H3K4me3 domains in mouse oocytes modulate maternal to zygotic transition. Dahl JA, Jung I, … Ren B, Klungland A. Nature, Online 12. September
-An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells. Vinogradova M, Gehling VS, …. Trojer P, Classon M. Nat Chem Biol. 2016 Jul;12(7):531-8
Suggested background reading:
Handbook of EPIGENETICS
Chapter 1 - Epigenetics: The New Science of Genetics, Pages 1-6
Chapter 2 - Mechanisms of DNA Methylation, Methyl-CpG Recognition, and Demethylation in Mammals, Pages 9-24
Chapter 3 - Mechanisms of Histone Modifications, Pages 25-45
Chapter 8 - Analysis of Gene-specific DNA Methylation, Pages 125-134
Chapter 9 - Methods for Assessing Genome-wide DNA Methylation, Pages 135-147
Chapter 10 - Methylation of Lysine 9 of Histone H3: Role of Heterochromatin Modulation and Tumorigenesis?, Pages 149-157
Chapter 11 - Chromatin Modifications Distinguish Genomic Features and Physical Organization of the Nucleus, Pages 159-171
Chapter 12 - Assessing Epigenetic Information, Pages 173-181
Chapter 15 - Mouse Models of Epigenetic Inheritance, Pages 233-249
Chapter 32 - Cancer Epigenetics, Pages 521-534
Chapter 36 - Imprinting Disorders in Humans, Pages 581-593
Chapter 37 - Clinical Applications of Histone Deacetylase Inhibitors, Pages 597-615