Osteoarthritis as an Enhanceropathy: Gene Regulation in Complex Musculoskeletal Disease

Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 2012;64:1697–707. https://doi.org/10.1002/art.34453.

Article  PubMed  PubMed Central  Google Scholar 

Steinmetz JD, Culbreth GT, Haile LM, Rafferty Q, Lo J, Fukutaki KG, et al. Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5:e508–22. https://doi.org/10.1016/S2665-9913(23)00163-7.

Article  Google Scholar 

Tachmazidou I, Hatzikotoulas K, Southam L, Esparza-Gordillo J, Haberland V, Zheng J, et al. Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019;51:230–6. https://doi.org/10.1038/S41588-018-0327-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aubourg G, Rice SJ, Bruce-Wootton P, Loughlin J. Genetics of osteoarthritis. Osteoarthritis Cartilage. 2021. https://doi.org/10.1016/j.joca.2021.03.002.

Article  PubMed  Google Scholar 

•• Boer CG, Hatzikotoulas K, Southam L, Stefánsdóttir L, Zhang Y, Coutinho de Almeida R, et al. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell. 2021;184:4784–4818.e17. https://doi.org/10.1016/J.CELL.2021.07.038. Report of the largest osteoarthritis GWAS to date, including cohorts from multiple ancestries.

Claringbould A, Zaugg JB. Enhancers in disease: molecular basis and emerging treatment strategies. Trends Mol Med. 2021;27:1060–73. https://doi.org/10.1016/J.MOLMED.2021.07.012.

Article  CAS  PubMed  Google Scholar 

Loughlin J. Three decades of osteoarthritis molecular genetics research: from early discussions to impressive breakthroughs. Osteoarthr Cartil. 2023. https://doi.org/10.1016/J.JOCA.2023.11.005.

Dempster ER, Lerner IM. Heritability of threshold characters. Genetics. 1950;35:212–36. https://doi.org/10.1093/GENETICS/35.2.212.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Erwin DH, Davidson EH. The evolution of hierarchical gene regulatory networks. Nat Rev Gen. 2009;10:141–8. https://doi.org/10.1038/nrg2499.

Article  CAS  Google Scholar 

Panigrahi A, O’Malley BW. Mechanisms of enhancer action: the known and the unknown. Genome Biol. 2021;22:1–30. https://doi.org/10.1186/S13059-021-02322-1.

Article  Google Scholar 

Wittkopp PJ, Kalay G. Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence. Nat Rev Gen. 2011;13:59–69. https://doi.org/10.1038/nrg3095.

Article  CAS  Google Scholar 

Panigrahi A, O’Malley BW. Mechanisms of enhancer action: the known and the unknown. Genome Biol. 2021; 22. https://doi.org/10.1186/S13059-021-02322-1.

Blackwood EM, Kadonaga JT. Going the distance: a current view of enhancer action. Science. 1979;1998(281):60–3. https://doi.org/10.1126/SCIENCE.281.5373.60/ASSET/2618B8F1-0EA6-459B-87E7-234ABBCC6EED/ASSETS/GRAPHIC/SE2886647005.JPEG.

Article  Google Scholar 

• Smith E, Shilatifard A. Enhancer biology and enhanceropathies. Nat Struct Mol Biol. 2014;21:210–9. https://doi.org/10.1038/nsmb.2784. First definition of the term “enhanceropathy” and discussion of enhancers in disease biology.

Article  CAS  PubMed  Google Scholar 

Gillies SD, Morrison SL, Oi VT, Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983;33:717–28. https://doi.org/10.1016/0092-8674(83)90014-4.

Article  CAS  PubMed  Google Scholar 

Banerji J, Olson L, Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983;33:729–40. https://doi.org/10.1016/0092-8674(83)90015-6.

Article  CAS  PubMed  Google Scholar 

Miyake N, Koshimizu E, Okamoto N, Mizuno S, Ogata T, Nagai T, et al. MLL2 and KDM6A mutations in patients with Kabuki syndrome. Am J Med Genet A. 2013;161:2234–43. https://doi.org/10.1002/AJMG.A.36072.

Article  CAS  Google Scholar 

Zimmermann N, Ferrer Acosta AMB, Kohlhase J, Bartsch O. Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome. Eur J Hum Genet. 2007;15:837–42. https://doi.org/10.1038/sj.ejhg.5201791.

Article  CAS  PubMed  Google Scholar 

Corradin O, Saiakhova A, Akhtar-Zaidi B, Myeroff L, Willis J, Cowper-Sallari R, et al. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Res. 2014;24:1–13. https://doi.org/10.1101/GR.164079.113.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Villicaña S, Bell JT. Genetic impacts on DNA methylation: research findings and future perspectives. Genome Biol. 2021;22:1–35. https://doi.org/10.1186/S13059-021-02347-6.

Article  Google Scholar 

Wolf SF, Jolly DJ, Lunnen KD, Friedmann T, Migeon BR. Methylation of the hypoxanthine phosphoribosyltransferase locus on the human X chromosome: implications for X-chromosome inactivation. Proc Natl Acad Sci U S A. 1984;81:2806–10. https://doi.org/10.1073/PNAS.81.9.2806.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Schübeler D. Function and information content of DNA methylation. Nature. 2015;517:321–6. https://doi.org/10.1038/NATURE14192.

Article  ADS  PubMed  Google Scholar 

Sharifi-Zarchi A, Gerovska D, Adachi K, Totonchi M, Pezeshk H, Taft RJ, et al. DNA methylation regulates discrimination of enhancers from promoters through a H3K4me1-H3K4me3 seesaw mechanism. BMC Genom. 2017;18:1–21. https://doi.org/10.1186/S12864-017-4353-7/FIGURES/6.

Article  Google Scholar 

Alajem A, Roth H, Ratgauzer S, Bavli D, Motzik A, Lahav S, et al. DNA methylation patterns expose variations in enhancer-chromatin modifications during embryonic stem cell differentiation. PLoS Genet. 2021;17:e1009498–e1009498. https://doi.org/10.1371/JOURNAL.PGEN.1009498.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Kreibich E, Kleinendorst R, Barzaghi G, Kaspar S, Krebs AR. Single-molecule footprinting identifies context-dependent regulation of enhancers by DNA methylation. Mol Cell. 2023;83:787-802.e9. https://doi.org/10.1016/J.MOLCEL.2023.01.017. Description of functional consequence of enhancer methylation in cell-type specific context.

Article  CAS  PubMed  Google Scholar 

Van Dongen J, Nivard MG, Willemsen G, Hottenga JJ, Helmer Q, Dolan CV, et al. Genetic and environmental influences interact with age and sex in shaping the human methylome. Nat Commun. 2016;7:1–13. https://doi.org/10.1038/ncomms11115.

Article  CAS  Google Scholar 

Hannon E, Knox O, Sugden K, Burrage J, Wong CCY, Belsky DW, et al. Characterizing genetic and environmental influences on variable DNA methylation using monozygotic and dizygotic twins. PLoS Genet. 2018;14:e1007544. https://doi.org/10.1371/JOURNAL.PGEN.1007544.

Article  PubMed  PubMed Central  Google Scholar 

Bell JT, Tsai PC, Yang TP, Pidsley R, Nisbet J, Glass D, et al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 2012;8:e1002629. https://doi.org/10.1371/JOURNAL.PGEN.1002629.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rowlatt A, Hernández-Suárez G, Sanabria-Salas MC, Serrano-López M, Rawlik K, Hernandez-Illan E, et al. The heritability and patterns of DNA methylation in normal human colorectum. Hum Mol Genet. 2016;25:2600–11. https://doi.org/10.1093/HMG/DDW072.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rushton MD, Reynard LN, Barter MJ, Refaie R, Rankin KS, Young DA, et al. Characterization of the cartilage DNA methylome in knee and hip osteoarthritis. Arthritis Rheumatol. 2014;66:2450–60. https://doi.org/10.1002/ART.38713/ABSTRACT.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rice SJ, Tselepi M, Sorial AK, Aubourg G, Shepherd C, Almarza D, et al. Prioritization of PLEC and GRINA as osteoarthritis risk genes through the identification and characterization of novel methylation quantitative trait loci. Arthritis Rheumatol. 2019;71:1285–96. https://doi.org/10.1002/ART.40849/ABSTRACT.

Article  CAS  PubMed  PubMed Central  Google Scholar 

• Rice SJ, Brumwell A, Falk J, Kehayova YS, Casement J, Parker E, et al. Genetic risk of osteoarthritis operates during human skeletogenesis. Hum Mol Genet. 2023;32:2124–38. https://doi.org/10.1093/HMG/DDAC251. Description of OA-mQTLs present in human foetal cartilage.

Article  PubMed  Google Scholar 

Rice SJ, Cheung K, Reynard LN, Loughlin J. Discovery and analysis of methylation quantitative trait loci (mQTLs) mapping to novel osteoarthritis genetic risk signals. Osteoarthr Cartil. 2019;27:1545–56. https://doi.org/10.1016/J.JOCA.2019.05.017.

Article  CAS  Google Scholar 

Kreitmaier P, Suderman M, Southam L, Coutinho de Almeida R, Hatzikotoulas K, Meulenbelt I, et al. An epigenome-wide view of osteoarthritis in primary tissues. Am J Hum Genet. 2022; 109: 1255–71. https://doi.org/10.1016/J.AJHG.2022.05.010.

Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, et al. High density DNA methylation array with single CpG site resolution. Genomics. 2011;98:288–95. https://doi.org/10.1016/J.YGENO.2011.07.007.

Article  CAS  PubMed  Google Scholar 

Kreitmaier P, Park Y-C, Swift D, Gilly A, Wilkinson JM, Zeggini E, et al. Epigenomic profiling of the infrapatellar fat pad in osteoarthritis. Hum Mol Genet. 2023. https://doi.org/10.1093/HMG/DDAD198.

Article  PubMed  Google Scholar 

Kehayova YS, Watson E, Wilkinson JM, Loughlin J, Rice SJ. Genetic and epigenetic interplay within a COLGALT2 enhancer associated with osteoarthritis. Arthritis Rheumatol. 2021;73:1856–65.

留言 (0)

沒有登入
gif