Imprinted Genes Impact Upon Beta Cell Function in the Current (and Potentially Next) Generation

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2021 May 14

PMID 33986727

Citations 2

Authors

Chelsie Villanueva-Hayes

Steven J Millership

Affiliations

Soon will be listed here.

Abstract

Beta cell failure lies at the centre of the aetiology and pathogenesis of type 2 diabetes and the epigenetic control of the expression of critical beta cell genes appears to play a major role in this decline. One such group of epigenetically-controlled genes, termed 'imprinted' genes, are characterised by transgenerational monoallelic expression due to differential allelic DNA methylation and play key functional roles within beta cells. Here, we review the evidence for this functional importance of imprinted genes in beta cells as well as their nutritional regulation by the diet and their altered methylation and/or expression in rodent models of diabetes and in type 2 diabetic islets. We also discuss imprinted genes in the context of the next generation, where dietary overnutrition in the parents can lead to their deregulation in the offspring, alongside beta cell dysfunction and defective glucose handling. Both the modulation of imprinted gene expression and the likelihood of developing type 2 diabetes in adulthood are susceptible to the impact of nutritional status in early life. Imprinted , therefore, represent an excellent opportunity with which to assess epigenomic changes in beta cells due to the diet in both the current and next generation.

Citing Articles

Differential CpG methylation at Nnat in the early establishment of beta cell heterogeneity.

Yu V, Yong F, Marta A, Khadayate S, Osakwe A, Bhattacharya S Diabetologia. 2024; 67(6):1079-1094.

PMID: 38512414 PMC: 11058053. DOI: 10.1007/s00125-024-06123-6.

Differential CpG methylation at in the early establishment of beta cell heterogeneity.

Yu V, Yong F, Marta A, Khadayate S, Osakwe A, Bhattacharya S bioRxiv. 2023; .

PMID: 38076935 PMC: 10705251. DOI: 10.1101/2023.02.04.527050.

References

Tobi E, Lumey L, Talens R, Kremer D, Putter H, Stein A . DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009; 18(21):4046-53. PMC: 2758137. DOI: 10.1093/hmg/ddp353. View

Bird A, Taggart M, Smith B . Methylated and unmethylated DNA compartments in the sea urchin genome. Cell. 1979; 17(4):889-901. DOI: 10.1016/0092-8674(79)90329-5. View

Arboleda V, Lee H, Parnaik R, Fleming A, Banerjee A, Ferraz-de-Souza B . Mutations in the PCNA-binding domain of CDKN1C cause IMAGe syndrome. Nat Genet. 2012; 44(7):788-92. PMC: 3386373. DOI: 10.1038/ng.2275. View

Shepherd R, Cosgrove K, OBrien R, Barnes P, Ammala C, Dunne M . Hyperinsulinism of infancy: towards an understanding of unregulated insulin release. European Network for Research into Hyperinsulinism in Infancy. Arch Dis Child Fetal Neonatal Ed. 2000; 82(2):F87-97. PMC: 1721057. DOI: 10.1136/fn.82.2.f87. View

Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D . The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med. 2000; 133(3):176-82. DOI: 10.7326/0003-4819-133-3-200008010-00008. View

Ou K, Yu M, Moss N, Wang Y, Wang A, Nguyen S . Targeted demethylation at the CDKN1C/p57 locus induces human β cell replication. J Clin Invest. 2018; 129(1):209-214. PMC: 6307972. DOI: 10.1172/JCI99170. View

John R, Lefebvre L . Developmental regulation of somatic imprints. Differentiation. 2011; 81(5):270-80. DOI: 10.1016/j.diff.2011.01.007. View

Arnaud P . Genomic imprinting in germ cells: imprints are under control. Reproduction. 2010; 140(3):411-23. DOI: 10.1530/REP-10-0173. View

Millership S, Van de Pette M, Withers D . Genomic imprinting and its effects on postnatal growth and adult metabolism. Cell Mol Life Sci. 2019; 76(20):4009-4021. PMC: 6785587. DOI: 10.1007/s00018-019-03197-z. View

10.

Heijmans B, Tobi E, Stein A, Putter H, Blauw G, Susser E . Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008; 105(44):17046-9. PMC: 2579375. DOI: 10.1073/pnas.0806560105. View

11.

Lee M, Reynisdottir I, Massague J . Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution. Genes Dev. 1995; 9(6):639-49. DOI: 10.1101/gad.9.6.639. View

12.

Kuo M, Mandel J, Chambon P . DNA methylation: correlation with DNase I sensitivity of chicken ovalbumin and conalbumin chromatin. Nucleic Acids Res. 1979; 7(8):2105-13. PMC: 342373. DOI: 10.1093/nar/7.8.2105. View

13.

Rutter G, Pullen T, Hodson D, Martinez-Sanchez A . Pancreatic β-cell identity, glucose sensing and the control of insulin secretion. Biochem J. 2015; 466(2):203-18. DOI: 10.1042/BJ20141384. View

14.

Cedar H, Bergman Y . Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet. 2009; 10(5):295-304. DOI: 10.1038/nrg2540. View

15.

Holt L, Lyons R, Ryan A, Beale S, Ward A, Cooney G . Dual ablation of Grb10 and Grb14 in mice reveals their combined role in regulation of insulin signaling and glucose homeostasis. Mol Endocrinol. 2009; 23(9):1406-14. PMC: 2737556. DOI: 10.1210/me.2008-0386. View

16.

Ravelli G, Stein Z, SUSSER M . Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976; 295(7):349-53. DOI: 10.1056/NEJM197608122950701. View

17.

Heindel J, Vandenberg L . Developmental origins of health and disease: a paradigm for understanding disease cause and prevention. Curr Opin Pediatr. 2015; 27(2):248-53. PMC: 4535724. DOI: 10.1097/MOP.0000000000000191. View

18.

Borges K, Arboleda V, Vilain E . Mutations in the PCNA-binding site of CDKN1C inhibit cell proliferation by impairing the entry into S phase. Cell Div. 2015; 10:2. PMC: 4389716. DOI: 10.1186/s13008-015-0008-8. View

19.

Stoger R, Kubicka P, Liu C, Kafri T, Razin A, Cedar H . Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell. 1993; 73(1):61-71. DOI: 10.1016/0092-8674(93)90160-r. View

20.

Font de Mora J, Esteban L, Burks D, Nunez A, Garces C, Garcia-Barrado M . Ras-GRF1 signaling is required for normal beta-cell development and glucose homeostasis. EMBO J. 2003; 22(12):3039-49. PMC: 162132. DOI: 10.1093/emboj/cdg280. View