1.
Miska, E. A. & Ferguson-Smith, A. C. Transgenerational inheritance: Models and
mechanisms of non-DNA sequence-based inheritance. Science 354, 59–63 (2016).
2.
Danchin, É. et al. Beyond DNA: Integrating inclusive inheritance into an extended
theory of evolution. Nature Reviews Genetics vol. 12 475–486 (2011).
3.
GURDON, J. B. The developmental capacity of nuclei taken from intestinal epithelium
cells of feeding tadpoles. J. Embryol. Exp. Morphol. 10, (1962).
4.
Thakore, P. I., Black, J. B., Hilton, I. B. & Gersbach, C. A. Editing the epigenome:
technologies for programmable transcription and epigenetic modulation. Nat.
Methods 13, 127–137 (2016).
5.
Zhou, V. W., Goren, A. & Bernstein, B. E. Charting histone modifications and the
functional organization of mammalian genomes. Nat. Rev. Genet. 12, 7–18 (2011).
6.
Greenberg, M. V. C. & Bourc’his, D. The diverse roles of DNA methylation in
mammalian development and disease. Nat. Rev. Mol. Cell Biol. 20, 590–607 (2019).
7.
Reinberg, D. & Vales, L. D. Chromatin domains rich in inheritance. Science (80-. ).
361, 33–34 (2018).
8.
Henikoff, S. & Greally, J. M. Epigenetics, cellular memory and gene regulation.
Current Biology vol. 26 R644–R648 (2016).
9.
D’Urso, A. & Brickner, J. H. Mechanisms of epigenetic memory. Trends in Genetics
vol. 30 230–236 (2014).
10.
Gangisetty, O. & Murugan, S. Epigenetic Modifications in Neurological Diseases:
Natural Products as Epigenetic Modulators a Treatment Strategy. in 1–25 (2016).
doi:10.1007/978-3-319-28383-8_1.
11.
Heard, E. & Martienssen, R. A. Transgenerational epigenetic inheritance: Myths and
mechanisms. Cell vol. 157 95–109 (2014).
12.
Perez, M. F. & Lehner, B. Intergenerational and transgenerational epigenetic
inheritance in animals. Nat. Cell Biol. 21, 143–151 (2019).
13.
Jablonka, E. & Raz, G. Transgenerational Epigenetic Inheritance: Prevalence,
Mechanisms, and Implications for the Study of Heredity and Evolution. Q. Rev. Biol.
84, 131–176 (2009).
14.
Landman, O. E. The Inheritance of Acquired Characteristics. Annu. Rev. Genet. 25,
1–20 (1991).
15.
Veenendaal, M. et al. Transgenerational effects of prenatal exposure to the 1944-45
Dutch famine. BJOG An Int. J. Obstet. Gynaecol. 120, 548–554 (2013).
55
16.
Waterland, R. A. & Jirtle, R. L. Transposable Elements: Targets for Early Nutritional
Effects on Epigenetic Gene Regulation. Mol. Cell. Biol. 23, 5293–5300 (2003).
17.
Duhl, D. M. J., Vrieling, H., Miller, K. A., Wolff, G. L. & Barsh, G. S. Neomorphic
agouti mutations in obese yellow mice. Nat. Genet. 8, 59–65 (1994).
18.
Tobi, E. W. et al. DNA methylation signatures link prenatal famine exposure to growth
and metabolism. Nat. Commun. 5, 5592 (2014).
19.
Feder, A., Nestler, E. J. & Charney, D. S. Psychobiology and molecular genetics of
resilience. Nat. Rev. Neurosci. 10, 446–457 (2009).
20.
Manning, K. et al. A naturally occurring epigenetic mutation in a gene encoding an
SBP-box transcription factor inhibits tomato fruit ripening. Nat. Genet. 38, 948–952
(2006).
21.
Cubas, P., Vincent, C. & Coen, E. An epigenetic mutation responsible for natural
variation in floral symmetry. Nature 401, 157–161 (1999).
22.
Teperek, M. et al. Sperm is epigenetically programmed to regulate gene transcription
in embryos. Genome Res. 26, 1034–1046 (2016).
23.
Siklenka, K. et al. Disruption of histone methylation in developing sperm impairs
offspring health transgenerationally. Science (80-. ). 350, aab2006–aab2006 (2015).
24.
Lesch, B. J. et al. Intergenerational epigenetic inheritance of cancer susceptibility in
mammals. Elife 8, (2019).
25.
Morgan, M. A. J. & Shilatifard, A. Reevaluating the roles of histone-modifying
enzymes and their associated chromatin modifications in transcriptional regulation.
Nat. Genet. 52, 1271–1281 (2020).
26.
Xia, W. & Xie, W. Rebooting the Epigenomes during Mammalian Early
Embryogenesis. Stem Cell Reports 15, 1158–1175 (2020).
27.
Fukushima, H. S., Takeda, H. & Nakamura, R. Targeted in vivo epigenome editing of
H3K27me3. Epigenetics Chromatin 12, 17 (2019).
28.
Ichikawa, K. et al. Centromere evolution and CpG methylation during vertebrate
speciation. Nat. Commun. 8, 1833 (2017).
29.
Qu, W. et al. Genome-wide genetic variations are highly correlated with proximal
DNA methylation patterns. Genome Res. 22, 1419–1425 (2012).
30.
Nakamura, R. et al. Large hypomethylated domains serve as strong repressive
machinery for key developmental genes in vertebrates. Development 141, 2568–
2580 (2014).
31.
Takeda, H. & Shimada, A. The Art of Medaka Genetics and Genomics: What Makes
56
Them So Unique? Annu. Rev. Genet. 44, 217–241 (2010).
32.
Bhandari, R. K. Medaka as a model for studying environmentally induced epigenetic
transgenerational inheritance of phenotypes. Environ. Epigenetics 2, (2016).
33.
Bhandari, R. K., vom Saal, F. S. & Tillitt, D. E. Transgenerational effects from early
developmental exposures to bisphenol A or 17α-ethinylestradiol in medaka, Oryzias
latipes. Sci. Rep. 5, 9303 (2015).
34.
Kungulovski, G. & Jeltsch, A. Epigenome Editing: State of the Art, Concepts, and
Perspectives. Trends in Genetics vol. 32 101–113 (2016).
35.
Steffen, P. A. & Ringrose, L. What are memories made of? How Polycomb and
Trithorax proteins mediate epigenetic memory. Nat. Rev. Mol. Cell Biol. 15, 340–356
(2014).
36.
Barnes, P. J., Adcock, I. M. & Ito, K. Histone acetylation and deacetylation:
Importance in inflammatory lung diseases. European Respiratory Journal vol. 25
552–563 (2005).
37.
Di Croce, L. & Helin, K. Transcriptional regulation by Polycomb group proteins. Nat.
Struct. Mol. Biol. 20, 1147–1155 (2013).
38.
Blackledge, N. P., Rose, N. R. & Klose, R. J. Targeting Polycomb systems to regulate
gene expression: modifications to a complex story. Nat. Rev. Mol. Cell Biol. 16, 643–
649 (2015).
39.
Cooper, S. et al. Targeting Polycomb to Pericentric Heterochromatin in Embryonic
Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment. Cell Rep. 7, 1456–
1470 (2014).
40.
Blackledge, N. P. et al. Variant PRC1 complex-dependent H2A ubiquitylation drives
PRC2 recruitment and polycomb domain formation. Cell 157, 1445–1459 (2014).
41.
Riising, E. M. et al. Gene silencing triggers polycomb repressive complex 2
recruitment to CpG Islands genome wide. Mol. Cell 55, 347–360 (2014).
42.
Schuettengruber, B., Bourbon, H.-M., Di Croce, L. & Cavalli, G. Genome Regulation
by Polycomb and Trithorax: 70 Years and Counting. Cell 171, 34–57 (2017).
43.
Schuettengruber, B., Chourrout, D., Vervoort, M., Leblanc, B. & Cavalli, G. Genome
Regulation by Polycomb and Trithorax Proteins. Cell vol. 128 735–745 (2007).
44.
Xiao, J. et al. Cis and trans determinants of epigenetic silencing by Polycomb
repressive complex 2 in Arabidopsis. Nat. Genet. 49, 1546–1552 (2017).
45.
Laprell, F., Finkl, K. & Müller, J. Propagation of Polycomb-repressed chromatin
requires sequence-specific recruitment to DNA. Science (80-. ). 356, 85–88 (2017).
57
46.
Coleman, R. T. & Struhl, G. Causal role for inheritance of H3K27me3 in maintaining
the OFF state of a Drosophila HOX gene. Science (80-. ). 356, eaai8236 (2017).
47.
Qi, L. S. et al. Repurposing CRISPR as an RNA-guided platform for sequencespecific control of gene expression. Cell 152, 1173–1183 (2013).
48.
Hilton, I. B. et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase
activates genes from promoters and enhancers. Nat. Biotechnol. 33, 510–517 (2015).
49.
Thakore, P. I. et al. Highly specific epigenome editing by CRISPR-Cas9 repressors
for silencing of distal regulatory elements. Nat. Methods 12, 1143–1149 (2015).
50.
Cano-Rodriguez, D. et al. Writing of H3K4Me3 overcomes epigenetic silencing in a
sustained but context-dependent manner. Nat. Commun. 7, 12284 (2016).
51.
Amabile, A. et al. Inheritable Silencing of Endogenous Genes by Hit-and-Run
Targeted Epigenetic Editing. Cell 167, 219-232.e14 (2016).
52.
Liu, X. S. et al. Editing DNA Methylation in the Mammalian Genome. Cell 167, 233247.e17 (2016).
53.
Morita, S. et al. Targeted DNA demethylation in vivo using dCas9–peptide repeat and
scFv–TET1 catalytic domain fusions. Nat. Biotechnol. 34, 1060–1065 (2016).
54.
Lin, S., Ewen-Campen, B., Ni, X., Housden, B. E. & Perrimon, N. In Vivo
Transcriptional Activation Using CRISPR/Cas9 in Drosophila. Genetics 201, 433–442
(2015).
55.
Jullien, J. et al. Gene Resistance to Transcriptional Reprogramming following Nuclear
Transfer Is Directly Mediated by Multiple Chromatin-Repressive Pathways. Mol. Cell
65, 873-884.e8 (2017).
56.
Yamazaki, T. et al. Targeted DNA methylation in pericentromeres with genome
editing-based artificial DNA methyltransferase. PLoS One 12, e0177764 (2017).
57.
Maeder, M. L. et al. CRISPR RNA–guided activation of endogenous human genes.
Nat. Methods 10, 977–979 (2013).
58.
Perez-Pinera, P. et al. RNA-guided gene activation by CRISPR-Cas9–based
transcription factors. Nat. Methods 10, 973–976 (2013).
59.
Lindeman, L. C. et al. Prepatterning of Developmental Gene Expression by Modified
Histones before Zygotic Genome Activation. Dev. Cell 21, 993–1004 (2011).
60.
Aizawa, K., Shimada, A., Naruse, K., Mitani, H. & Shima, A. The medaka midblastula
transition as revealed by the expression of the paternal genome. Gene Expr. Patterns
3, 43–47 (2003).
61.
Delvecchio, M., Gaucher, J., Aguilar-Gurrieri, C., Ortega, E. & Panne, D. Structure of
58
the p300 catalytic core and implications for chromatin targeting and HAT regulation.
Nat. Struct. Mol. Biol. 20, 1040–1046 (2013).
62.
Tropberger, P. et al. Regulation of Transcription through Acetylation of H3K122 on
the Lateral Surface of the Histone Octamer. Cell 152, 859–872 (2013).
63.
Nakamura, R., Uno, A., Kumagai, M., Morishita, S. & Takeda, H. Hypomethylated
domain-enriched DNA motifs prepattern the accessible nucleosome organization in
teleosts. Epigenetics Chromatin 10, 44 (2017).
64.
Wu, X. et al. Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian
cells. Nat Biotechnol 32, 670–676 (2014).
65.
Singh, R., Kuscu, C., Quinlan, A., Qi, Y. & Adli, M. Cas9-chromatin binding
information enables more accurate CRISPR off-target prediction. Nucleic Acids Res.
43, e118–e118 (2015).
66.
Brinkman, A. B. et al. Sequential ChIP-bisulfite sequencing enables direct genomescale investigation of chromatin and DNA methylation cross-talk. Genome Res. 22,
1128–1138 (2012).
67.
Wu, H. et al. Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates
Transcription of Neurogenic Genes. Science (80-. ). 329, 444–448 (2010).
68.
Tie, F. et al. CBP-mediated acetylation of histone H3 lysine 27 antagonizes
Drosophila Polycomb silencing. Development 136, 3131–3141 (2009).
69.
O’Geen, H. et al. dCas9-based epigenome editing suggests acquisition of histone
methylation is not sufficient for target gene repression. Nucleic Acids Res. 45, 9901–
9916 (2017).
70.
Souroullas, G. P. et al. An oncogenic Ezh2 mutation induces tumors through global
redistribution of histone 3 lysine 27 trimethylation. Nat. Med. 22, 632–640 (2016).
71.
Ezponda, T. & Licht, J. D. Molecular pathways: Deregulation of histone H3 lysine 27
methylation in cancer - Different paths, same destination. Clin. Cancer Res. 20,
5001–5008 (2014).
72.
Iwamatsu, T. Stages of normal development in the medaka Oryzias latipes. Mech.
Dev. 121, 605–618 (2004).
73.
Notredame, C., Higgins, D. G. & Heringa, J. T-coffee: a novel method for fast and
accurate multiple sequence alignment 1 1Edited by J. Thornton. J. Mol. Biol. 302,
205–217 (2000).
74.
Stothard, P. The Sequence Manipulation Suite: JavaScript Programs for Analyzing
and Formatting Protein and DNA Sequences. Biotechniques 28, 1102–1104 (2000).
59
75.
Stemmer, M., Thumberger, T., Del Sol Keyer, M., Wittbrodt, J. & Mateo, J. L. CCTop:
An intuitive, flexible and reliable CRISPR/Cas9 target prediction tool. PLoS One 10,
e0124633 (2015).
76.
Hwang, W. Y. et al. Efficient genome editing in zebrafish using a CRISPR-Cas
system. Nat. Biotechnol. 31, 227–229 (2013).
77.
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: A flexible trimmer for Illumina
sequence data. Bioinformatics 30, 2114–2120 (2014).
78.
Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler
transform. Bioinformatics 26, 589–595 (2010).
79.
Zhang, Y. et al. Model-based Analysis of ChIP-Seq (MACS). Genome Biol. 9, R137
(2008).
80.
Quinlan, A. R. & Hall, I. M. BEDTools: A flexible suite of utilities for comparing
genomic features. Bioinformatics 26, 841–842 (2010).
81.
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and
dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
82.
Chen, Q. et al. Sperm tsRNAs contribute to intergenerational inheritance of an
acquired metabolic disorder. Science (80-. ). 351, 397–400 (2016).
83.
Sharma, U. et al. Biogenesis and function of tRNA fragments during sperm
maturation and fertilization in mammals. Science (80-. ). 351, 391–396 (2016).
84.
Wang, X., Song, X. & Bhandari, R. K. Distinct expression patterns of seven crucial
microRNAs during early embryonic development in medaka (Oryzias latipes). Gene
Expr. Patterns 37, 119133 (2020).
85.
Jiang, L. et al. Sperm, but not oocyte, DNA methylome is inherited by zebrafish early
embryos. Cell 153, 773–784 (2013).
86.
Potok, M. E., Nix, D. A., Parnell, T. J. & Cairns, B. R. Reprogramming the maternal
zebrafish genome after fertilization to match the paternal methylation pattern. Cell
153, 759–772 (2013).
87.
Macleod, D., Clark, V. H. & Bird, A. Absence of genome-wide changes in DNA
methylation during development of the zebrafish. Nat. Genet. 23, 139–140 (1999).
88.
Veenstra, G. J. C. & Wolffe, A. P. Constitutive genomic methylation during embryonic
development of Xenopus. Biochim. Biophys. Acta - Gene Struct. Expr. 1521, 39–44
(2001).
89.
Murphy, P. J., Wu, S. F., James, C. R., Wike, C. L. & Cairns, B. R. Placeholder
Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming. Cell
60
172, 993-998.e13 (2018).
90.
Cheung, N. K. M. et al. Unlinking the methylome pattern from nucleotide sequence,
revealed by large-scale in vivo genome engineering and methylome editing in
medaka fish. PLOS Genet. 13, e1007123 (2017).
61
Acknowledgements
First of all, I would like to express my deepest gratitude for my supervisor, Professor Hiroyuki
Takeda, and my mentor (or trainer), Dr. Ryohei Nakamura, for providing me with the
opportunity to study in a splendid environment. They allowed me to proceed my challenging
Ph.D. project as I want to do and brought me irreplaceable experiences. I owe my completion
of my Ph.D. course to their substantial supports, encouragement, and patients.
I would like to express my gratitude to Dr. Tetsuji Kakutani for helpful discussion
about epigenetic inheritance among diverse species and giving me insightful comments.
Without his help, I would not have achieved to obtain Ph.D.
I would like to acknowledge all the lab members for everyday discussions and for
their continuous supports. Especially, I am grateful to lab alumni, Dr. Yasuko Isoe, Dr. Napo
K. M. Cheung and Dr. Kota Abe. They taught me a lot, through daily communications, about
very basic but important things which I should know to achieve Ph.D. and to be a good
scientist.
In addition, I would like to thank all my friends in Department of Biological Sciences
for encouraging me when I faced difficulties and for giving me constructive comments and
suggestions.
I would like to offer my special thanks to Jean-Baptiste Lamarck and Paul Kammerer.
Their classical but intriguing ideas and experiments motivated me and took me into this field
of epigenetics and inheritance. Without their previous contributions to science, I would never
know such a fascinating world.
Finally, I owe my gratitude to my family. They believed in me and encouraged me all
the time. I would like to dedicate this doctoral thesis to them.
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