A Comparative Methylome Analysis Reveals Conservation and Divergence of DNA Methylation Patterns and Functions in Vertebrates

Overview

Journal BMC Biol

Publisher Biomed Central

Specialty Biology

Date 2022 Mar 23

PMID 35317801

Authors

Hala Al Adhami

Anais Flore Bardet

Michael Dumas

Elouan Cleroux

Sylvain Guibert

Patricia Fauque

Herve Acloque

Michael Weber

Affiliations

Soon will be listed here.

Abstract

Background: Cytosine DNA methylation is a heritable epigenetic mark present in most eukaryotic groups. While the patterns and functions of DNA methylation have been extensively studied in mouse and human, their conservation in other vertebrates remains poorly explored. In this study, we interrogated the distribution and function of DNA methylation in primary fibroblasts of seven vertebrate species including bio-medical models and livestock species (human, mouse, rabbit, dog, cow, pig, and chicken).

Results: Our data highlight both divergence and conservation of DNA methylation patterns and functions. We show that the chicken genome is hypomethylated compared to other vertebrates. Furthermore, compared to mouse, other species show a higher frequency of methylation of CpG-rich DNA. We reveal the conservation of large unmethylated valleys and patterns of DNA methylation associated with X-chromosome inactivation through vertebrate evolution and make predictions of conserved sets of imprinted genes across mammals. Finally, using chemical inhibition of DNA methylation, we show that the silencing of germline genes and endogenous retroviruses (ERVs) are conserved functions of DNA methylation in vertebrates.

Conclusions: Our data highlight conserved properties of DNA methylation in vertebrate genomes but at the same time point to differences between mouse and other vertebrate species.

Citing Articles

Fundamentals of DNA methylation in development.

Gillespie C, Chowdhury A, Quinn K, Jenkins M, Rollins A, Watanabe M Pediatr Res. 2024; .

PMID: 39658604 DOI: 10.1038/s41390-024-03674-7.

Whole-genome DNA methylomes of tree shrew brains reveal conserved and divergent roles of DNA methylation on sex chromosome regulation.

Son D, Kong Y, Tan Y, Hu T, Shi L, Yi S BMC Biol. 2024; 22(1):277.

PMID: 39609804 PMC: 11603898. DOI: 10.1186/s12915-024-02071-0.

Unraveling the DNA methylation landscape in dog blood across breeds.

Nakamura M, Matsumoto Y, Yasuda K, Nagata M, Nakaki R, Okumura M BMC Genomics. 2024; 25(1):1089.

PMID: 39548380 PMC: 11566899. DOI: 10.1186/s12864-024-10963-2.

Epigenetics Research in Evolutionary Biology: Perspectives on Timescales and Mechanisms.

Yi S Mol Biol Evol. 2024; 41(9).

PMID: 39235767 PMC: 11376073. DOI: 10.1093/molbev/msae170.

Comprehensive Analysis of Methylome and Transcriptome to Identify Potential Genes Regulating Porcine Testis Development.

Feng Y, Zhang Y, Wu J, Qiao M, Zhou J, Xu Z Int J Mol Sci. 2024; 25(16).

PMID: 39201790 PMC: 11354776. DOI: 10.3390/ijms25169105.

References

Bird A . DNA methylation and the frequency of CpG in animal DNA. Nucleic Acids Res. 1980; 8(7):1499-504. PMC: 324012. DOI: 10.1093/nar/8.7.1499. View

Marzi S, Meaburn E, Dempster E, Lunnon K, Paya-Cano J, Smith R . Tissue-specific patterns of allelically-skewed DNA methylation. Epigenetics. 2016; 11(1):24-35. PMC: 4846124. DOI: 10.1080/15592294.2015.1127479. View

Schultz M, He Y, Whitaker J, Hariharan M, Mukamel E, Leung D . Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 2015; 523(7559):212-6. PMC: 4499021. DOI: 10.1038/nature14465. View

Zhang X, Nie Y, Cai S, Ding S, Fu B, Wei H . Earlier demethylation of myogenic genes contributes to embryonic precocious terminal differentiation of myoblasts in miniature pigs. FASEB J. 2019; 33(8):9638-9655. DOI: 10.1096/fj.201900388R. View

Langerman J, Lopez D, Pellegrini M, Smale S . Species-Specific Relationships between DNA and Chromatin Properties of CpG Islands in Embryonic Stem Cells and Differentiated Cells. Stem Cell Reports. 2021; 16(4):899-912. PMC: 8072027. DOI: 10.1016/j.stemcr.2021.02.016. View

Raddatz G, Arsenault R, Aylward B, Whelan R, Bohl F, Lyko F . A chicken DNA methylation clock for the prediction of broiler health. Commun Biol. 2021; 4(1):76. PMC: 7814119. DOI: 10.1038/s42003-020-01608-7. View

Xie W, Schultz M, Lister R, Hou Z, Rajagopal N, Ray P . Epigenomic analysis of multilineage differentiation of human embryonic stem cells. Cell. 2013; 153(5):1134-48. PMC: 3786220. DOI: 10.1016/j.cell.2013.04.022. View

Baubec T, Colombo D, Wirbelauer C, Schmidt J, Burger L, Krebs A . Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature. 2015; 520(7546):243-7. DOI: 10.1038/nature14176. View

Tukiainen T, Villani A, Yen A, Rivas M, Marshall J, Satija R . Landscape of X chromosome inactivation across human tissues. Nature. 2017; 550(7675):244-248. PMC: 5685192. DOI: 10.1038/nature24265. View

10.

Burger L, Gaidatzis D, Schubeler D, Stadler M . Identification of active regulatory regions from DNA methylation data. Nucleic Acids Res. 2013; 41(16):e155. PMC: 3763559. DOI: 10.1093/nar/gkt599. View

11.

Benton M, Lea R, Macartney-Coxson D, Sutherland H, White N, Kennedy D . Genome-wide allele-specific methylation is enriched at gene regulatory regions in a multi-generation pedigree from the Norfolk Island isolate. Epigenetics Chromatin. 2019; 12(1):60. PMC: 6781349. DOI: 10.1186/s13072-019-0304-7. View

12.

Okae H, Chiba H, Hiura H, Hamada H, Sato A, Utsunomiya T . Genome-wide analysis of DNA methylation dynamics during early human development. PLoS Genet. 2014; 10(12):e1004868. PMC: 4263407. DOI: 10.1371/journal.pgen.1004868. View

13.

de Mendoza A, Poppe D, Buckberry S, Pflueger J, Albertin C, Daish T . The emergence of the brain non-CpG methylation system in vertebrates. Nat Ecol Evol. 2021; 5(3):369-378. PMC: 7116863. DOI: 10.1038/s41559-020-01371-2. View

14.

Mugal C, Arndt P, Holm L, Ellegren H . Evolutionary consequences of DNA methylation on the GC content in vertebrate genomes. G3 (Bethesda). 2015; 5(3):441-7. PMC: 4349097. DOI: 10.1534/g3.114.015545. View

15.

Laurent L, Wong E, Li G, Huynh T, Tsirigos A, Ong C . Dynamic changes in the human methylome during differentiation. Genome Res. 2010; 20(3):320-31. PMC: 2840979. DOI: 10.1101/gr.101907.109. View

16.

Hackett J, Reddington J, Nestor C, Dunican D, Branco M, Reichmann J . Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline. Development. 2012; 139(19):3623-32. PMC: 3436114. DOI: 10.1242/dev.081661. View

17.

Choufani S, Shapiro J, Susiarjo M, Butcher D, Grafodatskaya D, Lou Y . A novel approach identifies new differentially methylated regions (DMRs) associated with imprinted genes. Genome Res. 2011; 21(3):465-76. PMC: 3044860. DOI: 10.1101/gr.111922.110. View

18.

Quenneville S, Verde G, Corsinotti A, Kapopoulou A, Jakobsson J, Offner S . 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. PMC: 3210328. DOI: 10.1016/j.molcel.2011.08.032. View

19.

Berletch J, Ma W, Yang F, Shendure J, Noble W, Disteche C . Escape from X inactivation varies in mouse tissues. PLoS Genet. 2015; 11(3):e1005079. PMC: 4364777. DOI: 10.1371/journal.pgen.1005079. View

20.

Babak T, Deveale B, Armour C, Raymond C, Cleary M, van der Kooy D . Global survey of genomic imprinting by transcriptome sequencing. Curr Biol. 2008; 18(22):1735-41. DOI: 10.1016/j.cub.2008.09.044. View