Santoro MR, Bray SM, Warren ST. Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol. 2012;7:219–45. doi:10.1146/annurev-pathol-011811-132457.
Article
CAS
PubMed
Google Scholar
Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A, et al. Advances in the treatment of fragile X syndrome. Pediatrics. 2009;123(1):378–90. doi:10.1542/peds.2008-0317.
Article
PubMed Central
PubMed
Google Scholar
Colak D, Zaninovic N, Cohen MS, Rosenwaks Z, Yang WY, Gerhardt J, et al. Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome. Science. 2014;343(6174):1002–5. doi:10.1126/science.1245831.
Article
PubMed Central
CAS
PubMed
Google Scholar
Fu YH, Kuhl DP, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, et al. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell. 1991;67(6):1047–58.
Article
CAS
PubMed
Google Scholar
Kenneson A, Zhang F, Hagedorn CH, Warren ST. Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers. Hum Mol Genet. 2001;10(14):1449–54.
Article
CAS
PubMed
Google Scholar
Tassone F, Hagerman PJ. Expression of the FMR1 gene. Cytogenet Genome Res. 2003;100(1-4):124–8. doi:72846.
Article
CAS
PubMed
Google Scholar
Willemsen R, Levenga J, Oostra BA. CGG repeat in the FMR1 gene: size matters. Clin Genet. 2011;80(3):214–25. doi:10.1111/j.1399-0004.2011.01723.x.
Article
PubMed Central
CAS
PubMed
Google Scholar
Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E, Hagerman RJ, et al. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci Transl Med. 2011;3(64):64ra1. doi:10.1126/scitranslmed.3001708.
Article
CAS
PubMed
Google Scholar
Hansen RS, Gartler SM, Scott CR, Chen SH, Laird CD. Methylation analysis of CGG sites in the CpG island of the human FMR1 gene. Hum Mol Genet. 1992;1(8):571–8.
Article
CAS
PubMed
Google Scholar
Sutcliffe JS, Nelson DL, Zhang F, Pieretti M, Caskey CT, Saxe D, et al. DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum Mol Genet. 1992;1(6):397–400.
Article
CAS
PubMed
Google Scholar
Bell MV, Hirst MC, Nakahori Y, MacKinnon RN, Roche A, Flint TJ, et al. Physical mapping across the fragile X: hypermethylation and clinical expression of the fragile X syndrome. Cell. 1991;64(4):861–6.
Article
CAS
PubMed
Google Scholar
Pietrobono R, Tabolacci E, Zalfa F, Zito I, Terracciano A, Moscato U, et al. Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet. 2005;14(2):267–77. doi:10.1093/hmg/ddi024.
Article
CAS
PubMed
Google Scholar
Coffee B, Zhang F, Ceman S, Warren ST, Reines D. Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile X syndrome. Am J Hum Genet. 2002;71(4):923–32. doi:10.1086/342931.
Article
PubMed Central
PubMed
Google Scholar
Tabolacci E, Neri G. Epigenetic modifications of the FMR1 gene. Methods Mol Biol. 2013;1010:141–53. doi:10.1007/978-1-62703-411-1_10.
Article
CAS
PubMed
Google Scholar
Kumari D, Usdin K. The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome. Hum Mol Genet. 2010;19(23):4634–42. doi:10.1093/hmg/ddq394.
Article
PubMed Central
CAS
PubMed
Google Scholar
Merenstein SA, Shyu V, Sobesky WE, Staley L, Berry-Kravis E, Nelson DL, et al. Fragile X syndrome in a normal IQ male with learning and emotional problems. J Am Acad Child Adolesc Psychiatry. 1994;33(9):1316–21. doi:10.1097/00004583-199411000-00014.
Article
CAS
PubMed
Google Scholar
Hagerman RJ, Hull CE, Safanda JF, Carpenter I, Staley LW, O'Connor RA, et al. High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. Am J Med Genet. 1994;51(4):298–308. doi:10.1002/ajmg.1320510404.
Article
CAS
PubMed
Google Scholar
Loesch D, Hagerman R. Unstable mutations in the FMR1 gene and the phenotypes. Adv Exp Med Biol. 2012;769:78–114.
Article
PubMed Central
CAS
PubMed
Google Scholar
Taylor AK, Safanda JF, Fall MZ, Quince C, Lang KA, Hull CE, et al. Molecular predictors of cognitive involvement in female carriers of fragile X syndrome. JAMA. 1994;271(7):507–14.
Article
CAS
PubMed
Google Scholar
Pretto D, Yrigollen CM, Tang HT, Williamson J, Espinal G, Iwahashi CK, et al. Clinical and molecular implications of mosaicism in FMR1 full mutations. Front Genet. 2014;5:318. doi:10.3389/fgene.2014.00318.
Article
PubMed Central
PubMed
Google Scholar
Godler DE, Tassone F, Loesch DZ, Taylor AK, Gehling F, Hagerman RJ, et al. Methylation of novel markers of fragile X alleles is inversely correlated with FMRP expression and FMR1 activation ratio. Hum Mol Genet. 2010;19(8):1618–32. doi:10.1093/hmg/ddq037.
Article
PubMed Central
CAS
PubMed
Google Scholar
Godler DE, Inaba Y, Shi EZ, Skinner C, Bui QM, Francis D, et al. Relationships between age and epi-genotype of the FMR1 exon 1/intron 1 boundary are consistent with non-random X-chromosome inactivation in FM individuals, with the selection for the unmethylated state being most significant between birth and puberty. Hum Mol Genet. 2013;22(8):1516–24. doi:10.1093/hmg/ddt002.
Article
PubMed Central
CAS
PubMed
Google Scholar
Tabolacci E, Moscato U, Zalfa F, Bagni C, Chiurazzi P, Neri G. Epigenetic analysis reveals a euchromatic configuration in the FMR1 unmethylated full mutations. European journal of human genetics : EJHG. 2008;16(12):1487–98. doi:10.1038/ejhg.2008.130.
Article
CAS
PubMed
Google Scholar
Tabolacci E, Pietrobono R, Moscato U, Oostra BA, Chiurazzi P, Neri G. Differential epigenetic modifications in the FMR1 gene of the fragile X syndrome after reactivating pharmacological treatments. European journal of human genetics : EJHG. 2005;13(5):641–8. doi:10.1038/sj.ejhg.5201393.
Article
CAS
PubMed
Google Scholar
Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324(5929):929–30. doi:10.1126/science.1169786.
Article
PubMed Central
CAS
PubMed
Google Scholar
Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–5. doi:10.1126/science.1170116.
Article
PubMed Central
CAS
PubMed
Google Scholar
Branco MR, Ficz G, Reik W. Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat Rev Genet. 2012;13(1):7–13. doi:10.1038/nrg3080.
CAS
Google Scholar
Szulwach KE, Li X, Li Y, Song CX, Wu H, Dai Q, et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci. 2011;14(12):1607–16. doi:10.1038/nn.2959.
Article
PubMed Central
CAS
PubMed
Google Scholar
Jin SG, Wu X, Li AX, Pfeifer GP. Genomic mapping of 5-hydroxymethylcytosine in the human brain. Nucleic Acids Res. 2011;39(12):5015–24. doi:10.1093/nar/gkr120.
Article
PubMed Central
CAS
PubMed
Google Scholar
Song CX, Szulwach KE, Fu Y, Dai Q, Yi C, Li X, et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol. 2011;29(1):68–72. doi:10.1038/nbt.1732.
Article
PubMed Central
CAS
PubMed
Google Scholar
Thomson JP, Lempiainen H, Hackett JA, Nestor CE, Muller A, Bolognani F, et al. Non-genotoxic carcinogen exposure induces defined changes in the 5-hydroxymethylome. Genome Biol. 2012;13(10):R93. doi:10.1186/gb-2012-13-10-r93.
Article
PubMed Central
CAS
PubMed
Google Scholar
Mellen M, Ayata P, Dewell S, Kriaucionis S, Heintz N. MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system. Cell. 2012;151(7):1417–30. doi:10.1016/j.cell.2012.11.022.
Article
PubMed Central
CAS
PubMed
Google Scholar
Khare T, Pai S, Koncevicius K, Pal M, Kriukiene E, Liutkeviciute Z, et al. 5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary. Nat Struct Mol Biol. 2012;19(10):1037–43. doi:10.1038/nsmb.2372.
Article
PubMed Central
CAS
PubMed
Google Scholar
Cheng Y, Bernstein A, Chen D, Jin P. 5-Hydroxymethylcytosine: a new player in brain disorders? Exp. Neurol.. 2014. doi:10.1016/j.expneurol.2014.05.008.
Al-Mahdawi S, Virmouni SA, Pook MA. The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases. Front Neurosci. 2014;8:397. doi:10.3389/fnins.2014.00397.
Article
PubMed Central
PubMed
Google Scholar
Szulwach KE, Li X, Li Y, Song CX, Han JW, Kim S, et al. Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLoS Genet. 2011;7(6):e1002154. doi:10.1371/journal.pgen.1002154.
Article
PubMed Central
CAS
PubMed
Google Scholar
Kinde B, Gabel HW, Gilbert CS, Griffith EC, Greenberg ME. Reading the unique DNA methylation landscape of the brain: non-CpG methylation, hydroxymethylation, and MeCP2. Proc Natl Acad Sci U S A. 2015. doi:10.1073/pnas.1411269112.
Maunakea AK, Nagarajan RP, Bilenky M, Ballinger TJ, D'Souza C, Fouse SD, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. 2010;466(7303):253–7.
Article
PubMed Central
CAS
PubMed
Google Scholar
Aman MG, Burrow WH, Wolford PL. The Aberrant Behavior Checklist-Community: factor validity and effect of subject variables for adults in group homes. American journal of mental retardation: AJMR. 1995;100(3):283–92.
CAS
PubMed
Google Scholar
Xie W, Dolzhanskaya N, LaFauci G, Dobkin C, Denman RB. Tissue and developmental regulation of fragile X mental retardation 1 exon 12 and 15 isoforms. Neurobiol Dis. 2009;35(1):52–62. doi:10.1016/j.nbd.2009.03.015.
Article
CAS
PubMed
Google Scholar
Verkerk AJ, de Graaff E, De Boulle K, Eichler EE, Konecki DS, Reyniers E, et al. Alternative splicing in the fragile X gene FMR1. Hum Mol Genet. 1993;2(4):399–404.
Article
CAS
PubMed
Google Scholar
Dolzhanskaya N, Bolton DC, Denman RB. Chemical and structural probing of the N-terminal residues encoded by FMR1 exon 15 and their effect on downstream arginine methylation. Biochemistry. 2008;47(33):8491–503. doi:10.1021/bi702298f.
Article
CAS
PubMed
Google Scholar
Ndlovu MN, Denis H, Fuks F. Exposing the DNA methylome iceberg. Trends Biochem Sci. 2011;36(7):381–7. doi:10.1016/j.tibs.2011.03.002.
CAS
PubMed
Google Scholar
Naumann A, Hochstein N, Weber S, Fanning E, Doerfler W. A distinct DNA-methylation boundary in the 5'- upstream sequence of the FMR1 promoter binds nuclear proteins and is lost in fragile X syndrome. Am J Hum Genet. 2009;85(5):606–16. doi:10.1016/j.ajhg.2009.09.018.
Article
PubMed Central
CAS
PubMed
Google Scholar
Guy J, Cheval H, Selfridge J, Bird A. The role of MeCP2 in the brain. Annu Rev Cell Dev Biol. 2011;27:631–52. doi:10.1146/annurev-cellbio-092910-154121.
Article
CAS
PubMed
Google Scholar
Wang T, Pan Q, Lin L, Szulwach KE, Song CX, He C, et al. Genome-wide DNA hydroxymethylation changes are associated with neurodevelopmental genes in the developing human cerebellum. Hum Mol Genet. 2012;21(26):5500–10. doi:10.1093/hmg/dds394.
Article
PubMed Central
CAS
PubMed
Google Scholar
Guo Y, Nady N, Qi C, Allali-Hassani A, Zhu H, Pan P, et al. Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2. Nucleic Acids Res. 2009;37(7):2204–10. doi:10.1093/nar/gkp086.
Article
PubMed Central
CAS
PubMed
Google Scholar
Kalakonda N, Fischle W, Boccuni P, Gurvich N, Hoya-Arias R, Zhao X, et al. Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1. Oncogene. 2008;27(31):4293–304. doi:10.1038/onc.2008.67.
Article
PubMed Central
CAS
PubMed
Google Scholar
Umlauf D, Goto Y, Feil R. Site-specific analysis of histone methylation and acetylation. Methods Mol Biol. 2004;287:99–120.
CAS
PubMed
Google Scholar
O'Geen H, Nicolet CM, Blahnik K, Green R, Farnham PJ. Comparison of sample preparation methods for ChIP-chip assays. Biotechniques. 2006;41(5):577–80.
Article
PubMed Central
PubMed
Google Scholar