BIOL 7800 (Section 3), Epigenetics, Fall 2014
Class: LSA663, 9:00-10:20 pm (Tuesday & Thursday)
Textbook: Epigenetics by C. David Allis et al, CSHL Press
Instructor: Dr. Joomyeong Kim, LSB room 644, 578-7692,
Office hours:By appointment.
Date Lecture Topics (Chapter Nos*)
August 26Overview of course
August 28DNA Methylation I (Ch 18, 6, 9)
September 2DNA Methylation II (Ch 18, 6, 9)
September 4Paper Discussion 1- Renee, Gapp et al (2014)
September 9(Writing Break)
September 11(Writing Break)
September 16Paper Discussion 2 – Joo Kim
September 18Histone Modification I (Ch 11)
September 23Histone Modification II (Ch 12)
September 25Histone Modification III (Ch 5)
September 30Paper Discussion 3 – Fabian, Lomniczi et al (2013)
October 2(Fall Break)
October 7Paper Discussion 4 – Jonathan, Jiang et al (2013)
October 9RNAi and Heterochromatin formation (Ch 8)
October 14Dosage Compensation (Ch 17, 16, 15)
October 16Genomic Imprinting (Ch 19)
October 21Paper Discussion 5 – Cody,Gregory Hannum et al. (2013)
October 23Paper Discussion 6 – Hannah, Martha Susiarjo et al. (2013),
Amanda, Peter Lewis et al 2013
October 28Paper Discussion 7 –Samantha, Jenkins et al (2014),
October 30Germ cells and Pluripotent Stem Cells (Ch 20, 22)
November 4Paper Discussion 8 - Vallmer, Ryan Lister et al. (2013)
November 6Paper Discussion 9– Dong, Smith ZD et al (2014)
November 11Epigenetics and Cancers (Ch 24)
November 13(Discussion and review of Proposals)
November 18(Discussion and review of Proposals)
November 20No class
November 25(Thanksgiving)
November 27(Thanksgiving)
*The students are required to read the textbook chapters in Bold-typed;
**The papers to be discussed during the Paper Discussion are accessible through the Pubmed.
During the beginning phase of the class, this course will cover three main mechanisms for epigenetics, DNA methylation, Histone Modification, RNAi-mediated heterochromatin formation. During the second phase of the class, this course will cover two main phenomena, X chromosome-related dosage compensation and Genomic imprinting as well as two closely related fields, Regenerative Medicine and Cancers. Each topic will be followed by the Discussion session covering recent breakthrough papers, which are listed below. For each discussion session, one or two students will present the main observation of each paper for the class. Each presentation will be evaluated by the other students (50% of the final score). For this class, the students also need to write one NIH-format proposal (5 -10 pages) covering their own research with possible epigenetic connection. There are two due dates for this proposal writing: the submission of the abstract will be Oct. 1st and the entire proposal will be Oct. 31st. Each written proposal will be distributed to three other students for the initial review, and later discussed and scored during the regular class (Nov 13&18). The evaluation score from the proposal will make up the remaining 50% of the final grade. The students are encouraged to discuss this writing with their advisors. This proposal could be used for potential submission to any fellowship award (NIH F31, NSF and private foundations).
The papers to be discussed in this course.
(2014 class)
Jenkins TG et al. (2014) Age-associated sperm DNA methylation alterations: possible implications in offspring disease susceptibility.PLoS Genet10(7):e1004458.
(DNA methylation versus age)
Smith ZD et al. (2014) DNA methylation dynamics of the human preimplantation embryo. Nature511: 611–615.
(DNA methylation in humans)
Smith ZD et al. (2012) A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature484(7394):339-344.
(DNA methylation in mice)
Guo H et al. (2014) The DNA methylation landscape of human early embryos. Nature511: 606–610.
(DNA methylation)
Radford et al. (2014) In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism.Science345(6198) DOI: 10.1126/science.125590
(DNA methylation versus nutrition)
Gapp K et al. (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nature Neuroscience17:667–669.
(Transgenerational inheritance of stress through small non-coding RNAs)
Kiskins E et al. (2014) Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1. Cell Stem Cell14(6): 781-195.
(Regenerative medicine and iPSC)
Jiang J et al. Translating dosage compensation to trisomy 21. (2013)Nature500(7462):296-300.
(Dosage compensation versus its application to the treatment of human genetic disorders)
(2013 class)
Ryan Lister et al. (2013) Global epigenomic reconfiguration during mammalian brain development. Science341: 1237905.
(DNA methylation)***
Kathryn Blaschke et al. (2013) Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature500: 222-226.
(DNA methylation and Stem cells and Environmental intervention)***
Gabriella Ficz et al. (2013) FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency. Cell Stem Cell13: 1-9.
(DNA demethylation and Regeneration medicine)***
Gregory Hannum et al. (2013) Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell49: 359-367.
(DNA methylation and aging)***
Diane I. Schroeder et al. (2013) The human placenta methylome. PNAS110: 6037-6042.
(DNA methylation)
Mingchao Xie et al. (2013) DNA hypomethylation within specific transposable element families associates with tissue-specific enhancer landscape. Nat Genet45: 836-841.
(DNA methylation)
Lavinia Gordon et al. (2012) Neonatal DNA methylation profile in human twins is specified by complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence. Genome Res22: 1395-1406.
(DNA methylation variations)
Martha Susiarjo et al. (2013) Bisphenol A exposure disrupts genomic imprinting in the mouse. Plos Genet9: e1003401.
(DNA methylation and environmental intervention)
Agnes Yu et al. (2013) Dynamic and biological relevance of DNA demethylatin in Arabidopsis antibacterial defense. PNAS110: 2389-2394.
(DNA methylation and non-mammalian system)
Fei Gao et al. (2012) Differential DNA methylation in discrete developmental stages of the parasitic nematode Trichinella spirallis. Genome Biology13: R100.
(DNA methylation and non-mammalian system)
Magdalena E. Potok et al. (2013) Reprogramming the maternal zebrafish genome after fertilization to match the paternal methylation pattern. Cell153: 759-772.
(DNA methylation reprogramming in zebrafish)
Yosef Bulganium et al. (2013) Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell150: 1209-1222.
(Regenerative medicine and cell reprogramming)
Jiang Zhu et al. (2013) Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell152: 642-654.
(Histone modification versus development)***
Svetlana Petruck et al. (2013) TrxG and PcG proteins but not methylated histones remain associated with DNA through replication. Cell150: 922-933.
(Histone modifications)***
Alejandro Lomniczi et al. (2013) Epigenetic control of female puberty. Nat Neurosci 16: 281-289.
(Histone modification and DNA methylation)
Peter W. Lewis et al. (2013) Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma. Science340: 857-861.
(Histone modification and Cancer)***
Andrzej T. Wierrzbicki et al. (2012) Spatial and functional relationships among Pol V-associated loci, Pol IV-dependent siRNAs, and cytosine methylation in the Arabidopsis epigenome. Genes Dev26: 1825-1836.
(siRNA-mediated DNA methylation)
Cathy C. Laurie et al. (2012) Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nat Genet44: 642-650.
(Cancer)
Szilvia Solyom et al. (2012) Extensive somatic L1 retrotransposition in colorectal tumors. Genome Res22: 2328-2338.
(Cancer)
Alasdair J.E. Gordon et al. (2013) Heritable change caused by transient transcription errors. Plos Genet9:e1003595.
(Epigenetics in E coli)
Jafar Kiani et al. (2013) RNA-mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2. Plos Genet9: e1003498.
(RNAi-mediated transgenerational inheritance in mice)***
Peter A. Jones (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Review Genet13: 484-492.
(Review)***
Li Shen and Yi Zhang (2013) 5-Hydroxymethycytosine: generation, fate, and genomic distribution. Curr Opin Cell Biol25: 289-296.
(review)***
Li Tan and Yujiang Geno Shi (2012) Tet family proteins and 5-hydroxymethylcytosine in development and disease. Development139: 1895-1902.
(review)***
Marianne Terndrup Pedersen and Kristian Helin (2010) Histone demethylation in development and disease. Trends Cell Biol20: 662-671.
(review)***
Agger et al. (2008) The emrging functions of histone demethylases. Curr Opin Genet Dev18: 159-168.
(review)***
Kathrin Plath and William E. Lowry (2011) Progress in understanding reprogramming to the induced pluripotent state. Nat Review Genet12: 253-265.
(Review)
Karen Adelman and John T. Lis (2012) Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans. Nat Review Genet13: 720-731.
(Review)
(2010 Class)
Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, Bell GW, Otte AP, Vidal M, Gifford DK, Young RA, Jaenisch R. (2006). Polycomb complexes repress developmental regulators in murine embryonic stem cells.Nature441, 349-353.
Cedar H, Bergman Y. (2009). Linking DNA methylation and histone modification: patterns and paradigms.Nat Rev Genet. 10, 295-304.
Ciccone, D.N., Su, H., Hevi, S., Gay, F., Lei, H., Bakjo, J., Xu, G., Li, E., and Chen, T. (2009). KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints. Nature461, 415-418.
Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.Nature 458,223-227.
Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM. (2000). CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus.
Nature405, 486-489.
Keshet I, Schlesinger Y, Farkash S, Rand E, Hecht M, Segal E, Pikarski E, Young RA, Niveleau A, Cedar H, Simon I. (2006). Evidence for an instructive mechanism of de novo methylation in cancer cells.Nat Genet. 38, 149-153.
Kim MS, Kondo T, Takada I, Youn MY, Yamamoto Y, Takahashi S, Matsumoto T, Fujiyama S, Shirode Y, Yamaoka I, Kitagawa H, Takeyama K, Shibuya H, Ohtake F, Kato S. (2009). DNA demethylation in hormone-induced transcriptional derepression.Nature461, 1007-1012.
Kono T, Obata Y, Wu Q, Niwa K, Ono Y, Yamamoto Y, Park ES, Seo JS, Ogawa H. (2004). Birth of parthenogenetic mice that can develop to adulthood.Nature428, 860-864.
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. (2009). Human DNA methylomes at base resolution show widespread epigenomic differences.Nature462, 315-322.
Meissner A, Mikkelsen TS, Gu H, Wernig M, Hanna J, Sivachenko A, Zhang X, Bernstein BE, Nusbaum C, Jaffe DB, Gnirke A, Jaenisch R, Lander ES. (2008). Genome-scale DNA methylation maps of pluripotent and differentiated cells.Nature454, 766-770.
Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G et al. (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature448, 553-560.
Ooi, S.K., Qiu, C., Bernstein, E., Li, K., Jia, D., Yang, Z., Erdjument-Bromage, H., Tempst, P., Lin, S.P., Allis, C.D., Cheng, X., and Bestor, T.H. (2007). DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature448, 714-717.
Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, Eden E, Yakhini Z, Ben-Shushan E, Reubinoff BE, Bergman Y, Simon I, Cedar H. (2007).
Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.Nat Genet. 39, 232-236.
Straussman R, Nejman D, Roberts D, Steinfeld I, Blum B, Benvenisty N, Simon I, Yakhini Z, Cedar H. (2009). Developmental programming of CpG island methylation profiles in the human genome.Nat Struct Mol Biol.16, 564-571.
Takahashi K, Yamanaka S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell126, 663-676.
Tilghman SM. (1999). The sins of the fathers and mothers: genomic imprinting in mammalian development.Cell96,185-193.