Transcription and chromatin determinants of de novo DNA methylation timing in oocytes
Tóm tắt
Gametogenesis in mammals entails profound re-patterning of the epigenome. In the female germline, DNA methylation is acquired late in oogenesis from an essentially unmethylated baseline and is established largely as a consequence of transcription events. Molecular and functional studies have shown that imprinted genes become methylated at different times during oocyte growth; however, little is known about the kinetics of methylation gain genome wide and the reasons for asynchrony in methylation at imprinted loci. Given the predominant role of transcription, we sought to investigate whether transcription timing is rate limiting for de novo methylation and determines the asynchrony of methylation events. Therefore, we generated genome-wide methylation and transcriptome maps of size-selected, growing oocytes to capture the onset and progression of methylation. We find that most sequence elements, including most classes of transposable elements, acquire methylation at similar rates overall. However, methylation of CpG islands (CGIs) is delayed compared with the genome average and there are reproducible differences amongst CGIs in onset of methylation. Although more highly transcribed genes acquire methylation earlier, the major transitions in the oocyte transcriptome occur well before the de novo methylation phase, indicating that transcription is generally not rate limiting in conferring permissiveness to DNA methylation. Instead, CGI methylation timing negatively correlates with enrichment for histone 3 lysine 4 (H3K4) methylation and dependence on the H3K4 demethylases KDM1A and KDM1B, implicating chromatin remodelling as a major determinant of methylation timing. We also identified differential enrichment of transcription factor binding motifs in CGIs acquiring methylation early or late in oocyte growth. By combining these parameters into multiple regression models, we were able to account for about a fifth of the variation in methylation timing of CGIs. Finally, we show that establishment of non-CpG methylation, which is prevalent in fully grown oocytes, and methylation over non-transcribed regions, are later events in oogenesis. These results do not support a major role for transcriptional transitions in the time of onset of DNA methylation in the oocyte, but suggest a model in which sequences least dependent on chromatin remodelling are the earliest to become permissive for methylation.
Tài liệu tham khảo
Bourc’his D, Xu G-L, Lin C-S, Bollman B, Bestor TH. Dnmt3L and the establishment of maternal genomic imprints. Science. 2001;294(5551):2536–9.
Branco MR, King M, Perez-Garcia V, Bogutz AB, Caley M, Fineberg E, Lefebvre L, Cook SJ, Dean W, Hemberger M, Reik W. Maternal DNA methylation regulates early trophoblast development. Dev Cell. 2016;36(2):152–63.
Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E, Sasaki H. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature. 2004;429(6994):900–3.
Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, Popp C, Thienpont B, Dean W, Reik W. The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell. 2012;48(6):849–62.
Kobayashi H, Sakurai T, Imai M, Takahashi N, Fukuda A, Yayoi O, Sato S, Nakabayashi K, Hata K, Sotomaru Y, Suzuki Y, Kono T. Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks. PLoS Genet. 2012;8(1):e1002440.
Veselovska L, Smallwood SA, Saadeh H, Stewart KR, Krueger F, Maupetit-Méhouas S, Arnaud P, Tomizawa S, Andrews S, Kelsey G. Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape. Genome Biol. 2015;16:209.
Smallwood SA, Tomizawa S, Krueger F, Ruf N, Carli N, Segonds-Pichon A, Sato S, Hata K, Andrews SR, Kelsey G. Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat Genet. 2011;43(8):811–4.
Chotalia M, Smallwood SA, Ruf N, Dawson C, Lucifero D, Frontera M, James K, Dean W, Kelsey G. Transcription is required for establishment of germline methylation marks at imprinted genes. Genes Dev. 2009;23(1):105–17.
Smith EY, Futtner CR, Chamberlain SJ, Johnstone KA, Resnick JL. Transcription is required to establish maternal imprinting at the Prader–Willi syndrome and Angelman syndrome locus. PLoS Genet. 2011;7(12):e1002422.
Stewart KR, Veselovska L, Kelsey G. Establishment and functions of DNA methylation in the germline. Epigenomics. 2016;8(10):1399–413.
Shirane K, Toh H, Kobayashi H, Miura F, Chiba H, Ito T, Kono T, Sasaki H. Mouse oocyte methylomes at base resolution reveal genome-wide accumulation of non-CpG methylation and role of DNA methyltransferases. PLoS Genet. 2013;9(4):e1003439.
Denomme MM, White CR, Gillio-Meina C, MacDonald WA, Deroo BJ, Kidder GM, Mann MRW. Compromised fertility disrupts Peg1 but not Snrpn and Peg3 imprinted methylation acquisition in mouse oocytes. Front Genet. 2012;3:129.
Hiura H, Obata Y, Komiyama J, Shirai M, Kono T. Oocyte growth-dependent progression of maternal imprinting in mice. Genes Cells. 2006;11(4):353–61.
Lucifero D, Mann MRW, Bartolomei MS, Trasler JM. Gene-specific timing and epigenetic memory in oocyte imprinting. Hum Mol Genet. 2004;13(8):839–49.
Obata Y, Kono T. Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth. J Biol Chem. 2002;277(7):5285–9.
Pan H, O’Brien MJ, Wigglesworth K, Eppig JJ, Schultz RM. Transcript profiling during mouse oocyte development and the effect of gonadotropin priming and development in vitro. Dev Biol. 2005;286(2):493–506.
Dhayalan A, Rajavelu A, Rathert P, Tamas R, Jurkowska RZ, Ragozin S, Jeltsch A. The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J Biol Chem. 2010;285(34):26114–20.
Ooi SK, Qiu C, Bernstein E, Li K, Jia D, Yang Z, Erdjument-Bromage H, Tempst P, Lin SP, Allis CD, Cheng X, Bestor TH. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature. 2007;448(7154):714–7.
Zhang Y, Jurkowska R, Soeroes S, Rajavelu A, Dhayalan A, Bock I, Rathert P, Brandt O, Reinhardt R, Fischle W, Jeltsch A. Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail. Nucleic Acids Res. 2010;38(13):4246–53.
Stewart KR, Veselovska L, Kim J, Huang J, Saadeh H, Tomizawa S, Smallwood SA, Chen T, Kelsey G. Dynamic changes in histone modifications precede de novo DNA methylation in oocytes. Genes Dev. 2015;29(23):2449–62.
Ciccone DN, Su H, Hevi S, Gay F, Lei H, Bajko J, Xu G-F, Li E, Chen T. KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints. Nature. 2009;461(7262):415–8.
Edmunds JW, Mahadevan LC, Clayton AL. Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J. 2008;27(2):406–20.
Kizer KO, Phatnani HP, Shibata Y, Hall H, Greenleaf AL, Strahl BD. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol Cell Biol. 2005;25(8):3305–16.
Yoh SM, Lucas JS, Jones KA. The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation. Genes Dev. 2008;22(24):3422–34.
Miura F, Enomoto Y, Dairiki R, Ito T. Amplification-free whole-genome bisulfite sequencing by post-bisulfite adaptor tagging. Nucleic Acids Res. 2012;40(17):e136.
Sookdeo A, Hepp CM, McClure MA, Boissinot S. Revisiting the evolution of mouse LINE-1 in the genomic era. Mob DNA. 2013;4:3.
Bulut-Karslioglu A, De La Rosa-Velazquez IA, Ramirez F, Barenboim M, Onishi-Seebacher M, Arand J, Galan C, Winter GE, Engist B, Gerle B, O’Sullivan RJ, Martens JHA, Walter J, Manke T, Lachner M, Jenuwein T. Suv39 h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells. Mol Cell. 2014;55(2):277–90.
Baubec T, Colombo DF, Wirbelauer C, Schmidt J, Burger L, Krebs AR, Akalin A, Schubeler D. Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature. 2015;520(7546):243–7.
Tomizawa S, Kobayashi H, Watanabe T, Andrews S, Hata K, Kelsey G, Sasaki H. Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes. Development. 2011;138(5):811–20.
Hara S, Takano T, Fujikawa T, Yamada M, Wakai T, Kono T, Obata Y. Forced expression of DNA methyltransferases during oocyte growth accelerates the establishment of methylation imprints but not functional genomic imprinting. Hum Mol Genet. 2014;23(14):3853–64.
Saadeh H, Schulz R. Protection of CpG islands against de novo DNA methylation during oogenesis is associated with the recognition site of E2f1 and E2f2. Epigenetics Chromatin. 2014;7:26.
Bailey TL. DREME: motif discovery in transcription factor ChIP-seq data. Bioinformatics. 2011;27(12):1653–9.
Bailey TL, Williams D, Misleh C, Li WW. MEME: discovering and analyzing DNA and protein sequence motifs. Nucleic Acids Res. 2006;34(suppl. 2):W369–73.
Ma P, de Waal E, Weaver JR, Bartolomei MS, Schultz RM. A DNMT3A2-HDAC2 complex is essential for genomic imprinting and genome integrity in mouse oocytes. Cell Rep. 2015;13(8):1552–60.
Quenneville S, Verde G, Corsinotti A, Kapopoulou A, Jakobsson J, Offner S, Baglivo I, Pedone PV, Grimaldi G, Riccio A, Trono D. In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions. Mol Cell. 2011;44(3):361–72.
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo Q-M, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009;462(7271):315–22.
Krueger F, Andrews SR. Bismark: a flexible aligner and methylation caller for bisulfite-seq applications. Bioinformatics. 2011;27(11):1571–2.
Gupta S, Stamatoyannopoulos JA, Bailey TL, Noble WS. Quantifying similarity between motifs. Genome Biol. 2007;8(2):R24.
Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z. GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics. 2009;10:48.