Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice

1. Eggermann T, Perez de Nanclares G, Maher ER, Temple IK, Tümer Z, Monk D, Mackay DJ, Grønskov K, Riccio A, Linglart A, Netchine I (2015) Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci. Clin Epigenetics 7: 123 doi: 10.1186/s13148-015-0143-8 26583054

2. Soellner L, Begemann M, Mackay DJ, Grønskov K, Tümer Z, Maher ER, Temple IK, Monk D, Riccio A, Linglart A, Netchine I, Eggermann T (2017) Recent Advances in Imprinting Disorders. Clin Genet 91: 3–13 doi: 10.1111/cge.12827 27363536

3. Barlow DP, Bartolomei MS (2014) Genomic imprinting in mammals. Cold Spring Harb Perspect Biol 1: 6–7

4. DeChiara TM, Efstratiadis A, Robertson EJ (1990) A growth deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 345: 78–80 doi: 10.1038/345078a0 2330056

5. O'Dell SD, Day IN (1998) Insulin-like growth factor II (IGF-II). Int J Biochem Cell Biol 30: 767–771 9722981

6. Sferruzzi-Perri AN, Sandovici I, Constancia M, Fowden AL (2017) Placental phenotype and the insulin-like growth factors: resource allocation to fetal growth. J Physiol 595: 5057–5093 doi: 10.1113/JP273330 28337745

7. Gabory A, Jammes H, Dandolo L (2010) The H19 locus: role of an imprinted non-coding RNA in growth and development. Bioessays 32: 473–480 doi: 10.1002/bies.200900170 20486133

8. Lui JC, Baron J (2013) Evidence that Igf2 down-regulation in postnatal tissues and up-regulation in malignancies is driven by transcription factor E2f3. Proc Natl Acad Sci USA 110: 6181–6186 doi: 10.1073/pnas.1219079110 23530192

9. Gicquel C, Rossignol S, Cabrol S, Houang M, Steunou V, Barbu V, Danton F, Thibaud N, Le Merrer M, Burglen L, Bertrand AM, Netchine I, Le Bouc Y (2005) Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome. Nat Genet 37: 1003–1007 doi: 10.1038/ng1629 16086014

10. Begemann M, Zirn B, Santen G, Wirthgen E, Soellner L, Büttel HM, Schweizer R, van Workum W, Binder G, Eggermann T (2015) Paternally Inherited IGF2 Mutation and Growth Restriction. N Engl J Med 373: 349–356 doi: 10.1056/NEJMoa1415227 26154720

11. Sparago A., Cerrato F., Vernucci M., Ferrero G.B., Cirillo-Silengo M. and Riccio A (2004) Microdeletions in the human H19 DMR result in loss of IGF2 imprinting and Beckwith-Wiedemann syndrome. Nat Genet 36: 958–960 doi: 10.1038/ng1410 15314640

12. Leighton PA, Saam JR, Ingram RS, Stewart CL, Tilghman SM (1995) An enhancer deletion affects both H19 and Igf2 expression. Genes Dev 9: 2079–2089 7544754

13. Ainscough JF, Koide T, Tada M, Barton S, Surani MA (1997) Imprinting of Igf2 and H19 from a 130 kb YAC transgene. Development 124: 3621–3632 9342054

14. Kaffer CR, Grinberg A, Pfeifer K (2001) Regulatory mechanisms at the mouse Igf2/H19 locus. Mol Cell Biol 21: 8189–8196 doi: 10.1128/MCB.21.23.8189-8196.2001 11689707

15. Davies K, Bowden L, Smith P, Dean W, Hill D, Furuumi H, Sasaki H, Cattanach B, Reik W (2002) Disruption of mesodermal enhancers for Igf2 in the minute mutant. Development 129: 1657–1668 11923202

16. 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. Nature 6785: 486–489

17. Bell AC, Felsenfeld G (2000) Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 6785: 482–485

18. Cerrato F, Sparago A, Di Matteo I, Zou X, Dean W, Sasaki H, Smith P, Genesio R, Bruggemann M, Reik W and Riccio A (2005) The two-domain hypothesis in Beckwith-Wiedemann Syndrome: Autonomous imprinting of the telomeric domain of the distal chromosome 7 cluster. Hum Mol Genet. 14: 503–511 doi: 10.1093/hmg/ddi047 15640248

19. Prawitt D, Enklaar T, Gartner-Rupprecht B, Spangenberg C, Oswald M, Lausch E, Schmidtke P, Reutzel D, Fees S, Lucito R, Korzon M, Brozek I, Limon J, Housman DE, Pelletier J and Zabel B (2005) Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor. Proc Natl Acad Sci USA 102: 4085–4090 doi: 10.1073/pnas.0500037102 15743916

20. Sparago A., Russo S., Cerrato F., Ferraiuolo S., Castorina P., Selicorni A., Schwienbacher C., Negrini M., Ferrero G.B., Silengo M.C., Anichini C., Larizza L., Riccio A (2007) Mechanisms causing imprinting defects in familial Beckwith–Wiedemann syndrome with Wilms' tumour. Hum Mol Genet 16: 254–264 doi: 10.1093/hmg/ddl448 17158821

21. Demars J, Shmela ME, Rossignol S, Okabe J, Netchine I, Azzi S, Cabrol S, Le Caignec C, David A, Le Bouc Y, El-Osta A, Gicquel C (2010) Analysis of the IGF2/H19 imprinting control region uncovers new genetic defects, including mutations of OCT-binding sequences, in patients with 11p15 fetal growth disorders. Hum Mol Genet 19: 803–814 doi: 10.1093/hmg/ddp549 20007505

22. De Crescenzo A, Coppola F, Falco P, Bernardo I, Ausanio G, Cerrato F, Falco L, Riccio A (2011) A novel microdeletion in the IGF2/H19 imprinting centre region defines a recurrent mutation mechanism in familial Beckwith-Wiedemann syndrome. Eur J Med Genet 54: 451–454

23. Poole RL, Leith DJ, Docherty LE, Shmela ME, Gicquel C, Splitt M, Temple IK, Mackay DJ (2012) Beckwith-Wiedemann syndrome caused by maternally inherited mutation of an OCT-binding motif in the IGF2/H19-imprinting control region, ICR1. Eur J Hum Genet 20: 240–243 doi: 10.1038/ejhg.2011.166 21863054

24. Berland S, Appelbäck M, Bruland O, Beygo J, Buiting K, Mackay DJ, Karen Temple I, Houge G (2013) Evidence for anticipation in Beckwith-Wiedemann syndrome. Eur J Hum Genet 21: 1344–1348 doi: 10.1038/ejhg.2013.71 23572028

25. Abi Habib W, Azzi S, Brioude F, Steunou V, Thibaud N, Das Neves C, Le Jule M, Chantot-Bastaraud S, Keren B, Lyonnet S, Michot C, Rossi M, Pasquier L, Gicquel C, Rossignol S, Le Bouc Y, Netchine I (2014) Extensive investigation of the IGF2/H19 imprinting control region reveals novel OCT4/SOX2 binding site defects associated with specific methylation patterns in Beckwith-Wiedemann syndrome. Hum Mol Genet 23: 5763–5773 doi: 10.1093/hmg/ddu290 24916376

26. Abi Habib W, Brioude F, Azzi S, Salem J, Das Neves C, Personnier C, Chantot-Bastaraud S, Keren B, Le Bouc Y, Harbison MD, Netchine I (2017) 11p15 ICR1 Partial Deletions Associated with IGF2/H19 DMR Hypomethylation and Silver-Russell Syndrome. Hum Mutat 38: 105–111 doi: 10.1002/humu.23131 27701793

27. Drewell RA, Brenton JD, Ainscough JF, Barton SC, Hilton KJ, Arney KL, Dandolo L, Surani MA (2000) Deletion of a silencer element disrupts H19 imprinting independently of a DNA methylation epigenetic switch. Development 127: 3419–3428 10903168

28. Thorvaldsen JL, Mann MR, Nwoko O, Duran KL, Bartolomei MS (2002) Analysis of sequence upstream of the endogenous H19 gene reveals elements both essential and dispensable for imprinting. Mol Cell Biol 22: 2450–2462. doi: 10.1128/MCB.22.8.2450-2462.2002 11909940

29. Schoenherr CJ, Levorse JM, Tilghman SM (2003) CTCF maintains differential methylation at the Igf2/H19 locus. Nat Genet 33: 66–69 doi: 10.1038/ng1057 12461525

30. Pant V, Mariano P, Kanduri C, Mattsson A, Lobanenkov V, Heuchel R, Ohlsson R (2003) The nucleotides responsible for the direct physical contact between the chromatin insulator protein CTCF and the H19 imprinting control region manifest parent of origin-specific long-distance insulation and methylation-free domains. Genes Dev 17: 586–590 doi: 10.1101/gad.254903 12629040

31. Pant V, Kurukuti S, Pugacheva E, Shamsuddin S, Mariano P, Renkawitz R, Klenova E, Lobanenkov V, Ohlsson R (2004) Mutation of a single CTCF target site within the H19 imprinting control region leads to loss of Igf2 imprinting and complex patterns of de novo methylation upon maternal inheritance. Mol Cell Biol 24: 3497–3504 doi: 10.1128/MCB.24.8.3497-3504.2004 15060168

32. Engel N, West AG, Felsenfeld G, Bartolomei M (2004) Antagonist between DNA hypermethylation and enhancer-blocking activity at the H19 DMD is uncovered by CpGg mutations. Nat Genet 36: 883–888 doi: 10.1038/ng1399 15273688

33. Engel N, Thorvaldsen JL, Bartolomei MS (2006) CTCF binding sites promote transcription initiation and prevent DNA methylation on the maternal allele at the imprinted H19/Igf2 locus. Hum Mol Genet 15: 2945–2954 doi: 10.1093/hmg/ddl237 16928784

34. Thorvaldsen JL, Fedoriw AM, Nguyen S, Bartolomei MS (2006) Developmental profile of H19 differentially methylated domain (DMD) deletion alleles reveals multiple roles of the DMD in regulating allelic expression and DNA methylation at the imprinted H19/Igf2 locus. Mol Cell Biol. 26: 1245–1258 doi: 10.1128/MCB.26.4.1245-1258.2006 16449639

35. Ideraabdullah FY, Thorvaldsen JL, Myers JA, Bartolomei MS (2014) Tissue-specific insulator function at H19/Igf2 revealed by deletions at the imprinting control region. Hum Mol Genet 23: 6246–6259 doi: 10.1093/hmg/ddu344 24990148

36. Beygo J, Citro V, Sparago A, De Crescenzo A, Cerrato F, Heitmann M, Rademacher K, Guala A, Enklaar T, Anichini C, Cirillo Silengo M, Graf N, Prawitt D, Vittoria Cubellis M, Horsthemke B, Buiting K, Riccio A (2013) The molecular function and clinical phenotype of partial deletions of the IGF2/H19 imprinting control region depends on the spatial arrangement of the remaining CTCF-binding sites. Hum Mol Genet 22: 544–57 doi: 10.1093/hmg/dds465 23118352

37. Hur SK, Freschi A, Ideraabdullah F, Thorvaldsen JL, Luense LJ, Weller AH, Berger SL, Cerrato F, Riccio A, Bartolomei MS (2016) Humanized H19/Igf2 locus reveals diverged imprinting mechanism between mouse and human and reflects Silver-Russell syndrome phenotypes. Proc Natl Acad Sci USA 113: 10938–10943 doi: 10.1073/pnas.1603066113 27621468

38. Wakeling EL, Brioude F, Lokulo-Sodipe O, O'Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Grønskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A et al, (2017) Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol 13: 105–124 doi: 10.1038/nrendo.2016.138 27585961

39. Mussa A, Russo S, Larizza L, Riccio A, Ferrero GB (2016) (Epi)genotype-phenotype correlations in Beckwith-Wiedemann syndrome: a paradigm for genomic medicine. Clin Genet 89: 403–415

40. Mussa A, Peruzzi L, Chiesa N, De Crescenzo A, Russo S, Melis D, Tarani L, Baldassarre G, Larizza L, Riccio A, Silengo M, Ferrero GB (2012) Nephrological findings and genotype-phenotype correlation in Beckwith-Wiedemann syndrome. Pediatr Nephrol 27: 397–406 doi: 10.1007/s00467-011-2009-4 22015620

41. Ginart P, Kalish JM, Jiang CL, Yu AC, Bartolomei MS, Raj A (2016) isualizing allele-specific expression in single cells reveals epigenetic mosaicism in an H19 loss-of-imprinting mutant. Genes Dev 30: 567–578 doi: 10.1101/gad.275958.115 26944681

42. Kühn R, Rajewsky K, Müller W (1991) Generation and analysis of interleukin-4 deficient mice. Science 254: 707–710 1948049

43. Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26: 99–109 10686599

44. Weyrich A (2012) Preparation of genomic DNA from mammalian sperm. Curr Protoc Mol Biol Chapter 2: Unit 2.13.1–3

45. Pedone PV, Pikaart MJ, Cerrato F, Vernucci M, Ungaro P, Bruni CB, Riccio A (1999) Role of histone acetylation and DNA methylation in the maintenance of the imprinted expression of the H19 and Igf2 genes. FEBS Lett 458: 45–50 10518931