دورية أكاديمية
أعرض في EDS

Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1.

التفاصيل البيبلوغرافية
العنوان: Screening for genes that accelerate the epigenetic aging clock in humans reveals a role for the H3K36 methyltransferase NSD1.
المؤلفون: Martin-Herranz DE; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. dem44@ebi.ac.uk.; Chronomics Ltd., Cambridge, UK. dem44@ebi.ac.uk., Aref-Eshghi E; Department of Pathology and Laboratory Medicine, Western University, London, Canada.; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, Canada., Bonder MJ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.; European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany., Stubbs TM; Chronomics Ltd., Cambridge, UK., Choufani S; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Canada., Weksberg R; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Canada., Stegle O; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.; European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.; Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany., Sadikovic B; Department of Pathology and Laboratory Medicine, Western University, London, Canada.; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, Canada., Reik W; Epigenetics Programme, The Babraham Institute, Cambridge, UK. wolf.reik@babraham.ac.uk.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. wolf.reik@babraham.ac.uk.; Wellcome Sanger Institute, Hinxton, Cambridge, UK. wolf.reik@babraham.ac.uk., Thornton JM; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. thornton@ebi.ac.uk.
المصدر: Genome biology [Genome Biol] 2019 Aug 14; Vol. 20 (1), pp. 146. Date of Electronic Publication: 2019 Aug 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 100960660 Publication Model: Electronic Cited Medium: Internet ISSN: 1474-760X (Electronic) Linking ISSN: 14747596 NLM ISO Abbreviation: Genome Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: London, UK : BioMed Central Ltd
Original Publication: London : Genome Biology Ltd., c2000-
مواضيع طبية MeSH: Epigenesis, Genetic* , Genetic Testing*, Aging/*genetics , Biological Clocks/*genetics , Histone-Lysine N-Methyltransferase/*genetics , Histones/*metabolism , Lysine/*metabolism, Adult ; CpG Islands/genetics ; DNA Methylation/genetics ; Entropy ; Genome, Human ; Humans ; Infant ; Models, Genetic ; Sotos Syndrome/genetics
مستخلص: Background: Epigenetic clocks are mathematical models that predict the biological age of an individual using DNA methylation data and have emerged in the last few years as the most accurate biomarkers of the aging process. However, little is known about the molecular mechanisms that control the rate of such clocks. Here, we have examined the human epigenetic clock in patients with a variety of developmental disorders, harboring mutations in proteins of the epigenetic machinery.
Results: Using the Horvath epigenetic clock, we perform an unbiased screen for epigenetic age acceleration in the blood of these patients. We demonstrate that loss-of-function mutations in the H3K36 histone methyltransferase NSD1, which cause Sotos syndrome, substantially accelerate epigenetic aging. Furthermore, we show that the normal aging process and Sotos syndrome share methylation changes and the genomic context in which they occur. Finally, we found that the Horvath clock CpG sites are characterized by a higher Shannon methylation entropy when compared with the rest of the genome, which is dramatically decreased in Sotos syndrome patients.
Conclusions: These results suggest that the H3K36 methylation machinery is a key component of the epigenetic maintenance system in humans, which controls the rate of epigenetic aging, and this role seems to be conserved in model organisms. Our observations provide novel insights into the mechanisms behind the epigenetic aging clock and we expect will shed light on the different processes that erode the human epigenetic landscape during aging.
References: Am J Hum Genet. 2017 May 4;100(5):773-788. (PMID: 28475860)
Genome Biol. 2016 Oct 3;17(1):205. (PMID: 27716309)
PLoS One. 2012;7(7):e41361. (PMID: 22848472)
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773. (PMID: 30357393)
Nature. 2015 Jan 15;517(7534):321-6. (PMID: 25592537)
J Infect Dis. 2015 Nov 15;212(10):1563-73. (PMID: 25969563)
Genome Res. 2010 Apr;20(4):440-6. (PMID: 20219944)
Nat Genet. 2019 Jan;51(1):96-105. (PMID: 30478443)
Epigenetics. 2017;12(11):923-933. (PMID: 28933623)
Bioinformatics. 2013 Jan 15;29(2):189-96. (PMID: 23175756)
Aging Cell. 2019 Feb;18(1):e12877. (PMID: 30450724)
Aging Cell. 2015 Jun;14(3):491-5. (PMID: 25678027)
Genome Biol. 2015 Jan 24;16:14. (PMID: 25616342)
BMC Bioinformatics. 2012 May 08;13:86. (PMID: 22568884)
Nat Rev Genet. 2018 Jun;19(6):371-384. (PMID: 29643443)
Am J Hum Genet. 2018 Jan 4;102(1):156-174. (PMID: 29304373)
Sci Rep. 2016 Nov 23;6:37393. (PMID: 27876760)
Bioinformatics. 2014 May 15;30(10):1363-9. (PMID: 24478339)
Genome Biol. 2017 Mar 28;18(1):57. (PMID: 28351423)
Cell. 2013 Jun 6;153(6):1194-217. (PMID: 23746838)
Aging (Albany NY). 2017 Apr;9(4):1143-1152. (PMID: 28377537)
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15538-43. (PMID: 25313081)
Cell. 2012 Jan 20;148(1-2):46-57. (PMID: 22265401)
Cell Metab. 2017 Apr 4;25(4):954-960.e6. (PMID: 28380383)
BMC Genomics. 2014 Dec 04;15:1062. (PMID: 25476734)
Aging (Albany NY). 2011 Oct;3(10):1018-27. (PMID: 22067257)
Aging (Albany NY). 2018 Oct 21;10(10):2832-2854. (PMID: 30348905)
Sci Rep. 2015 Aug 19;5:13107. (PMID: 26286994)
Genome Biol. 2016 Jun 06;17(1):122. (PMID: 27268795)
Aging (Albany NY). 2016 Jul;8(7):1485-512. (PMID: 27479945)
Genome Biol. 2017 Mar 28;18(1):58. (PMID: 28351383)
Nat Rev Mol Cell Biol. 2015 Oct;16(10):593-610. (PMID: 26373265)
Epigenomics. 2017 May;9(5):757-768. (PMID: 28517979)
Nat Genet. 2014 Jan;46(1):17-23. (PMID: 24270360)
Aging Cell. 2018 Jun;17(3):e12753. (PMID: 29573145)
Mol Cell. 2013 Jan 24;49(2):359-367. (PMID: 23177740)
Genome Biol. 2019 Dec 17;20(1):283. (PMID: 31847916)
Mol Ecol Resour. 2014 Sep;14(5):976-87. (PMID: 24606053)
Bioinformatics. 2011 Dec 15;27(24):3423-4. (PMID: 21949271)
Cell Stem Cell. 2016 Oct 6;19(4):491-501. (PMID: 27476967)
Nucleic Acids Res. 2017 Nov 16;45(20):11559-11569. (PMID: 29036576)
Sci Adv. 2016 Jul 29;2(7):e1600584. (PMID: 27482540)
Aging (Albany NY). 2017 Mar 28;9(3):1055-1068. (PMID: 28373601)
Nat Commun. 2015 Dec 22;6:10207. (PMID: 26690673)
Gene. 2017 Sep 5;627:337-342. (PMID: 28669924)
BMC Med Genet. 2013 Jan 29;14:18. (PMID: 23356558)
Genome Biol. 2017 Apr 11;18(1):68. (PMID: 28399939)
BMC Bioinformatics. 2016 Mar 08;17:120. (PMID: 26956433)
PLoS Comput Biol. 2007 Jun;3(6):e110. (PMID: 17559301)
Cell. 2006 Apr 21;125(2):315-26. (PMID: 16630819)
J Mol Diagn. 2016 Nov;18(6):834-841. (PMID: 27585064)
Genome Res. 2011 Sep;21(9):1426-37. (PMID: 21803857)
J Gerontol A Biol Sci Med Sci. 2019 Jan 1;74(1):57-61. (PMID: 29718110)
Genome Biol. 2016 Aug 11;17(1):171. (PMID: 27511193)
Clin Epigenetics. 2016 Jun 08;8:65. (PMID: 27279921)
Sci Rep. 2019 Mar 6;9(1):3770. (PMID: 30842553)
Epigenetics Chromatin. 2018 May 30;11(1):25. (PMID: 29848354)
Aging (Albany NY). 2016 Feb;8(2):394-401. (PMID: 26928272)
Elife. 2013 Feb 26;2:e00348. (PMID: 23467541)
Aging (Albany NY). 2015 May;7(5):334-9. (PMID: 25991677)
Genome Res. 2010 Apr;20(4):434-9. (PMID: 20219945)
Nat Commun. 2018 Jan 26;9(1):387. (PMID: 29374233)
Nucleic Acids Res. 2013 Apr;41(7):e90. (PMID: 23476028)
Nat Commun. 2016 Feb 02;7:10561. (PMID: 26830004)
Nature. 2012 Sep 6;489(7414):57-74. (PMID: 22955616)
Pediatr Neurol. 2009 May;40(5):357-64. (PMID: 19380072)
Mol Cell Biol. 2004 Oct;24(20):9048-58. (PMID: 15456878)
Hum Genet. 2015 Mar;134(3):317-332. (PMID: 25563730)
J Biol Chem. 2010 Aug 20;285(34):26114-20. (PMID: 20547484)
Mol Cell. 2018 Apr 19;70(2):371-379.e5. (PMID: 29606589)
Aging (Albany NY). 2018 Nov 27;10(11):3541-3557. (PMID: 30482885)
Genome Biol. 2015 Jan 30;16:25. (PMID: 25633388)
Aging (Albany NY). 2016 Sep 28;8(9):1844-1865. (PMID: 27690265)
Eur J Hum Genet. 2017 Dec;25(12):1335-1344. (PMID: 29255178)
Nature. 2017 Sep 14;549(7671):287-291. (PMID: 28869966)
Cell. 2013 May 23;153(5):1134-48. (PMID: 23664764)
Genome Biol. 2018 Feb 8;19(1):18. (PMID: 29422066)
Cell Rep. 2017 Jun 13;19(11):2371-2382. (PMID: 28614721)
Nat Genet. 2018 Apr;50(4):591-602. (PMID: 29610480)
Nat Genet. 2002 Apr;30(4):365-6. (PMID: 11896389)
Aging Cell. 2012 Apr;11(2):315-25. (PMID: 22212395)
Genome Biol. 2014 Dec 03;15(12):503. (PMID: 25599564)
Biostatistics. 2012 Jul;13(3):539-52. (PMID: 22101192)
Cell. 2016 Aug 11;166(4):822-839. (PMID: 27518561)
Mol Cell. 2013 Feb 7;49(3):571-82. (PMID: 23273982)
Nucleic Acids Res. 2015 Sep 18;43(16):e106. (PMID: 25990733)
Nature. 2017 Mar 2;543(7643):72-77. (PMID: 28225755)
Nature. 2015 Apr 9;520(7546):243-7. (PMID: 25607372)
Aging (Albany NY). 2018 Jul 26;10(7):1758-1775. (PMID: 30048243)
Mol Cell. 2018 Sep 20;71(6):882-895. (PMID: 30241605)
Genome Biol. 2016 Sep 22;17(1):191. (PMID: 27654999)
Genome Biol. 2013;14(10):R115. (PMID: 24138928)
Nat Rev Mol Cell Biol. 2012 Jan 23;13(2):115-26. (PMID: 22266761)
Genome Res. 2019 Jul;29(7):1057-1066. (PMID: 31160375)
Nature. 2019 Mar;567(7748):414-419. (PMID: 30867593)
Genes Dev. 2015 Jul 1;29(13):1362-76. (PMID: 26159996)
J Med Genet. 2014 Aug;51(8):512-7. (PMID: 24852293)
Epigenetics. 2013 Feb;8(2):203-9. (PMID: 23314698)
Genome Res. 2015 Oct;25(10):1473-81. (PMID: 26430157)
Elife. 2018 Nov 14;7:. (PMID: 30427307)
Genes Dev. 2015 Apr 1;29(7):718-31. (PMID: 25838541)
معلومات مُعتمدة: United Kingdom BB_ Biotechnology and Biological Sciences Research Council
فهرسة مساهمة: Keywords: Aging; Biological age; DNA methylation; Developmental disorder; Epigenetic clock; Epigenetics; H3K36 methylation; Methylation entropy; NSD1; Sotos syndrome
المشرفين على المادة: 0 (Histones)
EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
EC 2.1.1.43 (NSD1 protein, human)
K3Z4F929H6 (Lysine)
تواريخ الأحداث: Date Created: 20190815 Date Completed: 20200128 Latest Revision: 20231013
رمز التحديث: 20231013
مُعرف محوري في PubMed: PMC6693144
DOI: 10.1186/s13059-019-1753-9
PMID: 31409373
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-760X
DOI:10.1186/s13059-019-1753-9