Disruption of histone lysine methyltransferase genes and specific episignatures
https://doi.org/10.25557/2073-7998.2024.04.3-15
Abstract
Time-appropriate, stage-by-stage development of tissues and organs is achieved by coordinated operation of epigenetic mechanisms of gene expression regulation (DNA methylation, histone modifications, effects mediated by non-coding RNAs). It has been established that disruption of one single component of epigenetic regulation leads to changes in the functioning of others. Over the past 10 years there have been discovered more than 60 epigenomic signatures representing unique genome methylation patterns specific for hereditary disorders associated with disruption of the epigenetic machinery. The episignature can partially determine phenotypic traits and potentially serve as a reliable diagnostic tool due to its high specificity. This review aims to shed light on one of the central links of epigenetic regulation, histone methylation, as well as hereditary diseases that develop when it is disrupted, and the episignatures specific for these syndromes.
Supporting agencies: The research was carried out within the state assignment of Ministry of Science and Higher Education of the Russian Federation for RCMG.
About the Authors
O. A. Zemlianaia
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115478
A. V. Efremova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115478
I. V. Volodin
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115478
D. V. Zaletaev
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115478
References
1. Albini S., Zakharova V., Ait-Si-Ali S. Epigenetics and Regeneration, chapter 3 - Histone Modifications. [Internet]. Available from: https://doi.org/10.1016/B978-0-12-814879-2.00003-0.
2. Wood C., Snijders A., Williamson J., Reynolds C., Baldwin J., Dickman M. Post-translational modifications of the linker histone variants and their association with cell mechanisms. The FEBS Journal. 2009;276(13):3685-3697.
3. Millán-Zambrano G., Burton A., Bannister A.J., et al. Histone posttranslational modifications — cause and consequence of genome function. Nat Rev Genet. 2022;23:563–580.
4. Bannister A., Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381–395.
5. Greer E., Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012;13:343–357.
6. Litt M., Qiu Y., Huang S. Histone arginine methylations: their roles in chromatin dynamics and transcriptional regulation. Biosci Rep. 2009 Apr 1;29(2):131–141.
7. Hayashi T., Daitoku H., Uetake T., Kako K., Fukamizu A. Histidine Nτ-methylation identified as a new posttranslational modification in histone H2A at His-82 and H3 at His-39. The Journal of biological chemistry. 2023;299(9):105131.
8. Husmann D., Gozani O. Histone lysine methyltransferases in biology and disease. Nat Struct Mol Biol. 2019;26:880–889.
9. Falnes P.Ø., Małecki J.M., Herrera M.C., et al. Human seven-βstrand (METTL) methyltransferases - conquering the universe of protein lysine methylation. J Biol Chem. 2023;299(6):104661.
10. Wilson J.R., Jing C., Walker P.A. et al. Crystal structure and functional analysis of the histone methyltransferase SET7/9. Cell. 2002;111(1):105-115.
11. Dillon S.C., Zhang X., Trievel R.C., et al. The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol. 2005;(6):227.
12. Qian C., Zhou M.M. SET domain protein lysine methyltransferases: Structure, specificity and catalysis. Cell Mol Life Sci. 2006;63(23):2755-2763.
13. Smith B.C., Denu J.M. Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta. 2009;1789(1):45-57.
14. Kleefstra T., de Leeuw N. Kleefstra Syndrome. 2010 Oct 5 [Updated 2023 Jan 26]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK47079/.
15. Bonati M.T., Castronovo C., Sironi A., et al. 9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression. Neurogenetics. 2019;20(3):145-154.
16. Kleefstra T., Kramer J.M., Neveling K., et al. Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability. Am J Hum Genet. 2012;91(1):73-82.
17. Frega M., Selten M., Mossink B., et al. Distinct Pathogenic Genes Causing Intellectual Disability and Autism Exhibit a Common Neuronal Network Hyperactivity Phenotype. Cell Rep. 2020;30(1):173-186.e6.
18. Aref-Eshghi E., Kerkhof J., Pedro V.P., et al. Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders [published correction appears in Am J Hum Genet. 2021 Jun 3;108(6):1161-1163]. Am J Hum Genet. 2020;106(3):356-370.
19. Goodman S.J., Cytrynbaum C., Chung B.H.Y., et al. EHMT1 pathogenic variants and 9q34. 3 microdeletions share altered DNA methylation patterns in patients with Kleefstra syndrome. J Transl Genet Genom. 2020;4:144-58.
20. Adam M.P., Hudgins L., Hannibal M. Kabuki Syndrome. 2011 Sep 1 [Updated 2022 Sep 15]. In: Adam M.P., Feldman J., Mirzaa G.M., et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK62111/
21. Boniel S., Szymańska K., Śmigiel R., Szczałuba K. Kabuki Syndrome-Clinical Review with Molecular Aspects. Genes (Basel). 2021;12(4):468.
22. Van Laarhoven P.M., Neitzel L.R., Quintana A.M., et al. Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development. Hum Mol Genet. 2015;24(15):4443-4453.
23. Rose N.R., Klose R.J. Understanding the relationship between DNA methylation and histone lysine methylation. Biochim Biophys Acta. 2014;1839(12):1362-1372.
24. Aref-Eshghi E., Schenkel L.C., Lin H., et al. The defining DNA methylation signature of Kabuki syndrome enables functional assessment of genetic variants of unknown clinical significance. Epigenetics. 2017;12(11):923-933.
25. Jones W.D., Dafou D., McEntagart M., et al. De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am J Hum Genet. 2012;91(2):358-364.
26. Aggarwal A.., Rodriguez-Buritica D.F., Northrup H. WiedemannSteiner syndrome: Novel pathogenic variant and review of literature. Eur J Med Genet. 2017;60(6):285-288.
27. Milne T.A., Briggs S.D., Brock H.W., et al. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell. 2002;10(5):1107-1117.
28. Foroutan A., Haghshenas S., Bhai P., et al. Clinical Utility of a Unique Genome-Wide DNA Methylation Signature for KMT2ARelated Syndrome. Int. J. Mol. Sci. 2022;23(3):1815.
29. Weerts M.J.A., Lanko K., Guzmán-Vega F.J., et al. Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome. Genet Med. 2021;23(11):2122-2137.
30. Kranz A., Anastassiadis K. The role of SETD1A and SETD1B in development and disease. Biochim Biophys Acta Gene Regul Mech. 2020;1863(8):194578.
31. Krzyzewska I.M., Maas S.M., Henneman P., et al. A genome-wide DNA methylation signature for SETD1B-related syndrome. Clin Epigenetics. 2019;11(1):156.
32. Dhanoa B.S., Cogliati T., Satish A.G., et al. Update on the Kelchlike (KLHL) gene family. Hum Genomics. 2013;7(1):13.
33. Latour B.L., Van De Weghe J.C., Rusterholz T.D., et al. Dysfunction of the ciliary ARMC9/TOGARAM1 protein module causes Joubert syndrome. J Clin Invest. 2020;130(8):4423-4439.
34. Ocansey S., Tatton-Brown K. EZH2-Related Overgrowth. 2013 Jul 18 [Updated 2024 Mar 21]. In: Adam M.P., Feldman J., Mirzaa G.M,. et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK148820/
35. Liu P.P., Xu Y.J., Dai S.K., et al. Polycomb Protein EED Regulates Neuronal Differentiation through Targeting SOX11 in Hippocampal Dentate Gyrus. Stem Cell Rep. 2019;13(1):115-131.
36. Kim J.H., Lee J.H., Lee I.S., Lee S.B., Cho K.S. Histone Lysine Methylation and Neurodevelopmental Disorders. Int J Mol Sci. 2017;18(7):1404.
37. Cohen A.S., Tuysuz B., Shen Y., et al. A novel mutation in EED associated with overgrowth. J Hum Genet. 2015;60(6):339-342.
38. Viré E., Brenner C., Deplus R., et al. The Polycomb group protein EZH2 directly controls DNA methylation [published correction appears in Nature. 2007 Apr 12;446(7137):824]. Nature. 2006;439(7078):871-874.
39. Choufani S., Gibson W.T., Turinsky A.L., et al. DNA Methylation Signature for EZH2 Functionally Classifies Sequence Variants in Three PRC2 Complex Genes. Am J Hum Genet. 2020;106(5):596-610.
40. Awamleh Z., Goodman S., Choufani S., et al. DNA methylation signatures for chromatinopathies: current challenges and future applications. Hum Genet (2023).
41. Tatton-Brown K., Cole T.R.P., Rahman N.. Sotos Syndrome. 2004 Dec 17 [Updated 2022 Dec 1]. In: Adam M.P., Feldman J., Mirzaa G.M., et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1479/
42. Tauchmann S., Schwaller J. NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer. Life (Basel). 2021;11(9):877.
43. Faravelli F. NSD1 mutations in Sotos syndrome. Am J Med Genet C Semin Med Genet. 2005;137C(1):24-31.
44. Tauchmann S., Schwaller J. NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer. Life (Basel). 2021;11(9):877.
45. Weinberg D.N., Papillon-Cavanagh S., Chen H., et al. The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape. Nature. 2019;573(7773):281-286.
46. Choufani S., Cytrynbaum C., Chung B.H., et al. NSD1 mutations generate a genome-wide DNA methylation signature. Nat Commun. 2015;6:10207.
47. Xhabija B., Kidder B.L. KDM5B is a master regulator of the H3K4-methylome in stem cells, development and cancer. Semin Cancer Biol. 2019;57:79-85.
48. Wiel L.C., Bruno I., Barbi E., et al. From Wolf-Hirschhorn syndrome to NSD2 haploinsufficiency: a shifting paradigm through the description of a new case and a review of the literature. Ital J Pediatr. 2022;48(1):72.
49. Zollino M., Murdolo M., Marangi G., et al. On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Med Genet C Semin Med Genet. 2008;148C(4):257-269.
50. Zollino M., Doronzio P.N. Dissecting the Wolf–Hirschhorn syndrome phenotype: WHSC1 is a neurodevelopmental gene contributing to growth delay, intellectual disability, and to the facial dysmorphism. J Hum Genet. 2018;(63):859–861
51. Levy M.A., McConkey H., Kerkhof J., et al. Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders. HGG Adv. 2021;3(1):100075.
52. McConkey H., White-Brown A., Kerkhof J., et al. Genetically unresolved case of Rauch-Steindl syndrome diagnosed by its wolfhirschhorn associated DNA methylation episignature. Front Cell Dev Biol. 2022;10:1022683.
53. Sheppard S.E., Bryant L., Wickramasekara R.N., et al. Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice. Sci Adv. 2023;9(10):eade1463.
54. Ren W., Fan H., Grimm S.A. et al. DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation. Nat Commun. 2021;12:2490.
55. Butcher D.T., Cytrynbaum C., Turinsky A.L., et al. CHARGE and Kabuki Syndromes: Gene-Specific DNA Methylation Signatures Identify Epigenetic Mechanisms Linking These Clinically Overlapping Conditions. Am J Hum Genet. 2017;100(5):773-788.
56. Husson T., Lecoquierre F., Nicolas G., et al. Episignatures in practice: independent evaluation of published episignatures for the molecular diagnostics of ten neurodevelopmental disorders. Eur J Hum Genet. 2024;32:190–199.
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For citations:
Zemlianaia O.A., Efremova A.V., Volodin I.V., Zaletaev D.V. Disruption of histone lysine methyltransferase genes and specific episignatures. Medical Genetics. 2024;23(4):3-15. (In Russ.) https://doi.org/10.25557/2073-7998.2024.04.3-15
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