Genome-wide Methylation Analysis of Retrocopy-associated CpG Islands and Their Genomic Environment

Overview

Journal Epigenetics

Specialty Genetics

Date 2016 Feb 19

PMID 26890210

Citations 5

Authors

Katrin Grothaus

Deniz Kanber

Alexandra Gellhaus

Barbara Mikat

Julia Kolarova

Reiner Siebert

Dagmar Wieczorek

Bernhard Horsthemke

Affiliations

Soon will be listed here.

Abstract

Gene duplication by retrotransposition, i.e., the reverse transcription of an mRNA and integration of the cDNA into the genome, is an important mechanism in evolution. Based on whole-genome bisulfite sequencing of monocyte DNA, we have investigated the methylation state of all CpG islands (CGIs) associated with a retrocopy (n = 1,319), their genomic environment, as well as the CGIs associated with the ancestral genes. Approximately 10% of retrocopies are associated with a CGI. Whereas almost all CGIs of the human genome are unmethylated, 68% of the CGIs associated with a retrocopy are methylated. In retrocopies resulting from multiple retrotranspositions of the same ancestral gene, the methylation state of the CGI often differs. There is a strong positive correlation between the methylation state of the CGI/retrocopy and their genomic environment, suggesting that the methylation state of the integration site determined the methylation state of the CGI/retrocopy, or that methylation of the retrocopy by a host defense mechanism has spread into the adjacent regions. Only a minor fraction of CGI/retrocopies (n = 195) has intermediate methylation levels. Among these, the previously reported CGI/retrocopy in intron 2 of the RB1 gene (PPP1R26P1) as well as the CGI associated with the retrocopy RPS2P32 identified in this study carry a maternal methylation imprint. In conclusion, these findings shed light on the evolutionary dynamics and constraints of DNA methylation.

Citing Articles

Interruption of aberrant chromatin looping is required for regenerating RB1 function and suppressing tumorigenesis.

Wen X, Ding T, Li F, Fan J, Fan X, Jia R Commun Biol. 2022; 5(1):1036.

PMID: 36175480 PMC: 9522773. DOI: 10.1038/s42003-022-04007-2.

Evolutionary conservation of DNA methylation in CpG sites within ultraconserved noncoding elements.

Colwell M, Drown M, Showel K, Drown C, Palowski A, Faulk C Epigenetics. 2018; 13(1):49-60.

PMID: 29372669 PMC: 5836973. DOI: 10.1080/15592294.2017.1411447.

The maternal uniparental disomy of chromosome 6 (upd(6)mat) "phenotype": result of placental trisomy 6 mosaicism?.

Eggermann T, Oehl-Jaschkowitz B, Dicks S, Thomas W, Kanber D, Albrecht B Mol Genet Genomic Med. 2017; 5(6):668-677.

PMID: 29178649 PMC: 5702562. DOI: 10.1002/mgg3.324.

New insights into the imprinted MEG8-DMR in 14q32 and clinical and molecular description of novel patients with Temple syndrome.

Beygo J, Kuchler A, Gillessen-Kaesbach G, Albrecht B, Eckle J, Eggermann T Eur J Hum Genet. 2017; 25(8):935-945.

PMID: 28635951 PMC: 5567157. DOI: 10.1038/ejhg.2017.91.

Protein-Coding Genes' Retrocopies and Their Functions.

Kubiak M, Makalowska I Viruses. 2017; 9(4).

PMID: 28406439 PMC: 5408686. DOI: 10.3390/v9040080.

References

Zhang Z, Schwartz S, Wagner L, Miller W . A greedy algorithm for aligning DNA sequences. J Comput Biol. 2000; 7(1-2):203-14. DOI: 10.1089/10665270050081478. View

Mighell A, Smith N, Robinson P, Markham A . Vertebrate pseudogenes. FEBS Lett. 2000; 468(2-3):109-14. DOI: 10.1016/s0014-5793(00)01199-6. View

Chamberlain S, Brannan C . The Prader-Willi syndrome imprinting center activates the paternally expressed murine Ube3a antisense transcript but represses paternal Ube3a. Genomics. 2001; 73(3):316-22. DOI: 10.1006/geno.2001.6543. View

Chai J, Locke D, Ohta T, Greally J, Nicholls R . Retrotransposed genes such as Frat3 in the mouse Chromosome 7C Prader-Willi syndrome region acquire the imprinted status of their insertion site. Mamm Genome. 2002; 12(11):813-21. DOI: 10.1007/s00335-001-2083-1. View

Takai D, Jones P . Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A. 2002; 99(6):3740-5. PMC: 122594. DOI: 10.1073/pnas.052410099. View

Monk D, Bentley L, Beechey C, Hitchins M, Peters J, Preece M . Characterisation of the growth regulating gene IMP3, a candidate for Silver-Russell syndrome. J Med Genet. 2002; 39(8):575-81. PMC: 1735212. DOI: 10.1136/jmg.39.8.575. View

Zhang Z, Harrison P, Liu Y, Gerstein M . Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. Genome Res. 2003; 13(12):2541-58. PMC: 403796. DOI: 10.1101/gr.1429003. View

Karolchik D, Hinrichs A, Furey T, Roskin K, Sugnet C, Haussler D . The UCSC Table Browser data retrieval tool. Nucleic Acids Res. 2003; 32(Database issue):D493-6. PMC: 308837. DOI: 10.1093/nar/gkh103. View

Gunzburg W, Groner B . The chromosomal integration site determines the tissue-specific methylation of mouse mammary tumour virus proviral genes. EMBO J. 1984; 3(5):1129-35. PMC: 557485. DOI: 10.1002/j.1460-2075.1984.tb01941.x. View

10.

Jahner D, Jaenisch R . Retrovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity. Nature. 1985; 315(6020):594-7. DOI: 10.1038/315594a0. View

11.

Gardiner-Garden M, Frommer M . CpG islands in vertebrate genomes. J Mol Biol. 1987; 196(2):261-82. DOI: 10.1016/0022-2836(87)90689-9. View

12.

Rougeulle C, Glatt H, Lalande M . The Angelman syndrome candidate gene, UBE3A/E6-AP, is imprinted in brain. Nat Genet. 1997; 17(1):14-5. DOI: 10.1038/ng0997-14. View

13.

Liao B, Hu Y, Herrick D, Brewer G . The RNA-binding protein IMP-3 is a translational activator of insulin-like growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells. J Biol Chem. 2005; 280(18):18517-24. DOI: 10.1074/jbc.M500270200. View

14.

Landers M, Calciano M, Colosi D, Glatt-Deeley H, Wagstaff J, Lalande M . Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans. Nucleic Acids Res. 2005; 33(13):3976-84. PMC: 1178004. DOI: 10.1093/nar/gki705. View

15.

Vinckenbosch N, Dupanloup I, Kaessmann H . Evolutionary fate of retroposed gene copies in the human genome. Proc Natl Acad Sci U S A. 2006; 103(9):3220-5. PMC: 1413932. DOI: 10.1073/pnas.0511307103. View

16.

Rapkins R, Hore T, Smithwick M, Ager E, Pask A, Renfree M . Recent assembly of an imprinted domain from non-imprinted components. PLoS Genet. 2006; 2(10):e182. PMC: 1626109. DOI: 10.1371/journal.pgen.0020182. View

17.

Wood A, Roberts R, Monk D, Moore G, Schulz R, Oakey R . A screen for retrotransposed imprinted genes reveals an association between X chromosome homology and maternal germ-line methylation. PLoS Genet. 2007; 3(2):e20. PMC: 1796624. DOI: 10.1371/journal.pgen.0030020. View

18.

Suzuki S, Ono R, Narita T, Pask A, Shaw G, Wang C . Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting. PLoS Genet. 2007; 3(4):e55. PMC: 1851980. DOI: 10.1371/journal.pgen.0030055. View

19.

Royo H, Cavaille J . Non-coding RNAs in imprinted gene clusters. Biol Cell. 2008; 100(3):149-66. DOI: 10.1042/BC20070126. View

20.

Horsthemke B, Wagstaff J . Mechanisms of imprinting of the Prader-Willi/Angelman region. Am J Med Genet A. 2008; 146A(16):2041-52. DOI: 10.1002/ajmg.a.32364. View