Skip to main content

Advertisement

SpringerLink
Log in

Fetal environment, epigenetics, and pediatric renal disease

  • Educational Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The notion that some adult diseases may have their origins in utero has recently captured scientists’ attention. Some of these effects persist across generations and may involve epigenetic mechanisms. Epigenetic modifications, DNA methylation together with covalent modifications of histones, alter chromatin density and accessibility of DNA to cellular machinery, modulating the transcriptional potential of the underlying DNA sequence. Here, we will discuss the different epigenetic modifications and their potential role in and contribution to renal disease development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Wood AJ, Oakey RJ (2006) Genomic imprinting in mammals: emerging themes and established theories. PLoS Genet 2:e147

    Article  PubMed  Google Scholar 

  2. Knoll JH, Nicholls RD, Magenis RE, Graham JM Jr, Lalande M, Latt SA (1989) Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. Am J Med Genet 32:285–290

    Article  PubMed  CAS  Google Scholar 

  3. Knoll JH, Nicholls RD, Magenis RE, Glatt K, Graham JM Jr, Kaplan L, Lalande M (1990) Angelman syndrome: three molecular classes identified with chromosome 15q11q13-specific DNA markers. Am J Hum Genet 47:149–154

    PubMed  CAS  Google Scholar 

  4. Hong H, Takahashi K, Ichisaka T, Aoi T, Kanagawa O, Nakagawa M, Okita K, Yamanaka S (2009) Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460:1132–1135

    Article  PubMed  CAS  Google Scholar 

  5. Yamanaka S (2009) Elite and stochastic models for induced pluripotent stem cell generation. Nature 460:49–52

    Article  PubMed  CAS  Google Scholar 

  6. Yamanaka S (2009) A fresh look at iPS cells. Cell 137:13–17

    Article  PubMed  CAS  Google Scholar 

  7. Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4:143–153

    Article  PubMed  CAS  Google Scholar 

  8. Dressler GR (2008) Epigenetics, development, and the kidney. J Am Soc Nephrol 19:2060–2067

    Article  PubMed  CAS  Google Scholar 

  9. Pembrey ME, Bygren LO, Kaati G, Edvinsson S, Northstone K, Sjostrom M, Golding J (2006) Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14:159–166

    Article  PubMed  Google Scholar 

  10. Kaati G, Bygren LO, Pembrey M, Sjostrom M (2007) Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 15:784–790

    Article  PubMed  CAS  Google Scholar 

  11. Zandi-Nejad K, Luyckx VA, Brenner BM (2006) Adult hypertension and kidney disease: the role of fetal programming. Hypertension 47:502–508

    Article  PubMed  CAS  Google Scholar 

  12. Luyckx VA, Brenner BM (2005) Low birth weight, nephron number, and kidney disease. Kidney Int Suppl S68–S77

  13. Alexander BT (2003) Intrauterine growth restriction and reduced glomerular number: role of apoptosis. Am J Physiol Regul Integr Comp Physiol 285:R933–R934

    PubMed  CAS  Google Scholar 

  14. Hughson MD, Douglas-Denton R, Bertram JF, Hoy WE (2006) Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int 69:671–678

    Article  PubMed  CAS  Google Scholar 

  15. McGraw M, Poucell S, Sweet J, Baumal R (1984) The significance of focal segmental glomerulosclerosis in oligomeganephronia. Int J Pediatr Nephrol 5:67–72

    PubMed  CAS  Google Scholar 

  16. Hodgin JB, Rasoulpour M, Markowitz GS, D’Agati VD (2009) Very low birth weight is a risk factor for secondary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol 4:71–76

    Article  PubMed  Google Scholar 

  17. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2000) Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 342:381–389

    Google Scholar 

  18. Lopes-Virella MF, Carter RE, Gilbert GE, Klein RL, Jaffa M, Jenkins AJ, Lyons TJ, Garvey WT, Virella G (2008) Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications. Diab Care 31:2006–2012

    Article  CAS  Google Scholar 

  19. El-Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M (2008) Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med 205:2409–2417

    Article  PubMed  CAS  Google Scholar 

  20. Brasacchio D, Okabe J, Tikellis C, Balcerczyk A, George P, Baker EK, Calkin AC, Brownlee M, Cooper ME, El-Osta A (2009) Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that co-exist on the lysine tail. Diabetes 58:1229–1236

    Article  PubMed  CAS  Google Scholar 

  21. White NH, Sun W, Cleary PA, Danis RP, Davis MD, Hainsworth DP, Hubbard LD, Lachin JM, Nathan DM (2008) Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus: 10 years after the Diabetes Control and Complications Trial. Arch Ophthal 126:1707–1715

    Article  PubMed  Google Scholar 

  22. Dressler GR (2009) Advances in early kidney specification, development and patterning. Development 136:3863–3874

    Google Scholar 

  23. Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP (2005) Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell 9:283–292

    Article  PubMed  CAS  Google Scholar 

  24. Patel SR, Kim D, Levitan I, Dressler GR (2007) The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex. Dev Cell 13:580–592

    Article  PubMed  CAS  Google Scholar 

  25. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315–322

    Article  PubMed  CAS  Google Scholar 

  26. Fazzari MJ, Greally JM (2004) Epigenomics: beyond CpG islands. Nat Rev 5:446–455

    Article  CAS  Google Scholar 

  27. Chow J, Heard E (2009) X inactivation and the complexities of silencing a sex chromosome. Curr Opin Cell Biol 21:359–366

    Article  PubMed  CAS  Google Scholar 

  28. Agrelo R, Wutz A (2009) X inactivation and disease. Semin Cell Dev Biol 21:194–200

    PubMed  Google Scholar 

  29. Reik W, Dean W, Walter J (2001) Epigenetic reprogramming in mammalian development. Science 293:1089–1093

    Article  PubMed  CAS  Google Scholar 

  30. Razin A (1998) CpG methylation, chromatin structure and gene silencing-a three-way connection. EMBO J 17:4905–4908

    Article  PubMed  CAS  Google Scholar 

  31. Ho KL, McNae IW, Schmiedeberg L, Klose RJ, Bird AP, Walkinshaw MD (2008) MeCP2 binding to DNA depends upon hydration at methyl-CpG. Mol Cell 29:525–531

    Article  PubMed  CAS  Google Scholar 

  32. Lasalle JM, Yasui DH (2009) Evolving role of MeCP2 in Rett syndrome and autism. Epigenomics 1:119–130

    Article  PubMed  CAS  Google Scholar 

  33. Bechtel W, McGoohan S, Zeisberg EM, Muller GA, Kalbacher H, Salant DJ, Muller CA, Kalluri R, Zeisberg M (2010) Methylation determines fibroblast activation and fibrogenesis in the kidney. Nat Med 16:544–550

    Article  PubMed  CAS  Google Scholar 

  34. Einstein F, Thompson RF, Bhagat TD, Fazzari MJ, Verma A, Barzilai N, Greally JM (2010) Cytosine methylation dysregulation in neonates following intrauterine growth restriction. PLoS One 5:e8887

    Article  PubMed  Google Scholar 

  35. Marmorstein R, Trievel RC (2009) Histone modifying enzymes: structures, mechanisms, and specificities. Biochim Biophys Acta 1789:58–68

    PubMed  CAS  Google Scholar 

  36. Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412

    Article  PubMed  CAS  Google Scholar 

  37. Guil S, Esteller M (2009) DNA methylomes, histone codes and miRNAs: tying it all together. Int J Biochem Cell Biol 41:87–95

    Article  PubMed  CAS  Google Scholar 

  38. Sayyed SG, Gaikwad AB, Lichtnekert J, Kulkarni O, Eulberg D, Klussmann S, Tikoo K, Anders HJ (2010) Progressive glomerulosclerosis in type 2 diabetes is associated with renal histone H3K9 and H3K23 acetylation, H3K4 dimethylation and phosphorylation at serine 10. Nephrol Dial Transplant 25:1811–1817

    Article  PubMed  CAS  Google Scholar 

  39. Gaikwad AB, Sayyed SG, Lichtnekert J, Tikoo K, Anders HJ (2010) Renal failure increases cardiac histone h3 acetylation, dimethylation, and phosphorylation and the induction of cardiomyopathy-related genes in type 2 diabetes. Am J Pathol 176:1079–1083

    Article  PubMed  CAS  Google Scholar 

  40. Li Y, Reddy MA, Miao F, Shanmugam N, Yee JK, Hawkins D, Ren B, Natarajan R (2008) Role of the histone H3 lysine 4 methyltransferase, SET7/9, in the regulation of NF-kappaB-dependent inflammatory genes. Relevance to diabetes and inflammation. J Biol Chem 283:26771–26781

    Article  PubMed  CAS  Google Scholar 

  41. Villeneuve LM, Reddy MA, Lanting LL, Wang M, Meng L, Natarajan R (2008) Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes. Proc Natl Acad Sci USA 105:9047–9052

    Article  PubMed  CAS  Google Scholar 

  42. Pentz ES, Lopez ML, Kim HS, Carretero O, Smithies O, Gomez RA (2001) Ren1d and Ren2 cooperate to preserve homeostasis: evidence from mice expressing GFP in place of Ren1d. Physiol Genomics 6:45–55

    PubMed  CAS  Google Scholar 

  43. Gomez RA, Pentz ES, Jin X, Cordaillat M, Sequeira Lopez ML (2009) CBP and p300 are essential for renin cell identity and morphological integrity of the kidney. Am J Physiol Heart Circ Physiol 296:H1255–H1262

    Article  PubMed  CAS  Google Scholar 

  44. Bjornsson HT, Fallin MD, Feinberg AP (2004) An integrated epigenetic and genetic approach to common human disease. Trends Genet 20:350–358

    Article  PubMed  CAS  Google Scholar 

  45. Wilson AG (2008) Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases. J Periodontol 79:1514–1519

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank members of the Einstein Center for Epigenomics and the Susztak lab for the discussion. Our studies are supported by NIH 1R01DK087635 to KS.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Nephrology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Ullmann Bldg 619, Bronx, NY, 10461, USA

    Robert Woroniecki

  2. Department of Medicine, Division of Nephrology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Ullmann Bldg 619, Bronx, NY, 10461, USA

    Anil Bhanudas Gaikwad & Katalin Susztak

  3. Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Ullmann Bldg 619, Bronx, NY, 10461, USA

    Katalin Susztak

Authors
  1. Robert Woroniecki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anil Bhanudas Gaikwad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katalin Susztak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katalin Susztak.

Additional information

Answers:

1. c

2. e

3. d

4. e

5. d

Questions:

Questions:

Answers appear following the reference list.

  1. 1.

    Epigenetics (nongenetic causes of a phenotype) may involve processes of:

    1. a)

      Genetic imprinting

    2. b)

      Histone methylation

    3. c)

      Cytosine methylation

    4. d)

      RNA interference

    5. e)

      All of the above

  2. 2.

    Euchromatin denotes the region in where DNA undergoes

    1. a)

      Transcriptional activation

    2. b)

      Demethylation

    3. c)

      Methylation

    4. d)

      Gene silencing

    5. e)

      a and b

  3. 3.

    Active histone marks (H3K4me3 and H3K36me3) refer to:

    1. a)

      Euchromatin

    2. b)

      Trimethylation

    3. c)

      Heterochromatin

    4. d)

      a and b

    5. e)

      All of the above

  4. 4.

    The epigenetic modifications play a role in following diseases and physiologic processes:

    1. a)

      Cancer

    2. b)

      Organ development

    3. c)

      Fetal programming

    4. d)

      Diabetes

    5. e)

      All of the above

  5. 5.

    Differences in clinical phenotype between Prader-Willi and Angelman syndromes result from:

    1. a)

      Histone acetylation

    2. b)

      DNA demethylation

    3. c)

      Expression of micro RNAs

    4. d)

      Genetic imprinting

    5. e)

      All of the above

Rights and permissions

Reprints and permissions

About this article

Cite this article

Woroniecki, R., Gaikwad, A.B. & Susztak, K. Fetal environment, epigenetics, and pediatric renal disease. Pediatr Nephrol 26, 705–711 (2011). https://doi.org/10.1007/s00467-010-1714-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-010-1714-8

Keywords

Search

Navigation