The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Extensive changes in DNA methylation are associated with expression of mutant huntingtin
Open accessAbstract
The earliest stages of Huntington disease are marked by changes in gene expression that are caused in an indirect and poorly understood manner by polyglutamine expansions in the huntingtin (HTT) protein. To explore the hypothesis that DNA methylation may be altered in cells expressing mutated HTT, we use reduced representation bisulfite sequencing (RRBS) to map sites of DNA methylation in cells carrying either wild-type or mutant HTT. We find that a large fraction of the genes that change in expression in the presence of mutant huntingtin demonstrate significant changes in DNA methylation. Regions with low CpG content, which have previously been shown to undergo methylation changes in response to neuronal activity, are disproportionately affected. On the basis of the sequence of regions that change in methylation, we identify AP-1 and SOX2 as transcriptional regulators associated with DNA methylation changes, and we confirm these hypotheses using genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq). Our findings suggest new mechanisms for the effects of polyglutamine-expanded HTT. These results also raise important questions about the potential effects of changes in DNA methylation on neurogenesis and cognitive decline in patients with Huntington disease.
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Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556
Okano, M., Bell, D. W., Haber, D. A., & Li, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81656-6 · Cited by 6,143
Linking DNA methylation and histone modification: patterns and paradigms
Cedar, H., & Bergman, Y. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2540 · Cited by 2,267 · cited 1×
“Due to biochemical interactions betweenDNAmethyltransferases and SET domain histone methyltransferases (13), changes in repressive histone marks could result in changes in DNA methylation.”
BackgroundDNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation
Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., & Sun, Y. E. (2003) · Science · doi:10.1126/science.1090842 · Cited by 1,405
DNA-binding factors shape the mouse methylome at distal regulatory regions
Stadler, M. B., Murr, R., Burger, L., Ivanek, R., Lienert, F., Schöler, A., Nimwegen, E. V., Wirbelauer, C., Oakeley, E. J., Gaidatzis, D., et al. (2011) · Nature · doi:10.1038/nature10716 · Cited by 1,383
Cognitive disorders and neurogenesis deficits in Huntington’s disease mice are rescued by fluoxetine
Grote, H. E., Bull, N. D., Howard, M. L., Van Dellen, A., Blakemore, C., Bartlett, P. F., & Hannan, A. J. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04365.x · Cited by 179
Hogart, A., Lichtenberg, J., Ajay, S. S., Anderson, S., NIH Intramural Sequencing Center, Margulies, E. H., & Bodine, D. M. (2012) · Genome Research · doi:10.1101/gr.132878.111 · Cited by 101
Cited by
Huntington’s Disease: Mechanisms of Pathogenesis and Therapeutic Strategies
Jimenez-Sanchez, M., Licitra, F., Underwood, B. R., & Rubinsztein, D. C. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024240 · Cited by 507
The epigenetics of aging and neurodegeneration
Lardenoije, R., Iatrou, A., Kenis, G., Kompotis, K., Steinbusch, H. W. M., Mastroeni, D., Coleman, P., Lemere, C. A., Hof, P. R., van den Hove, D. L. A., et al. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.002 · Cited by 381
Oxidative Stress and Huntington’s Disease: The Good, the Bad, and the Ugly
Kumar, A., & Ratan, R. R. (2016) · Journal of Huntington s Disease · doi:10.3233/jhd-160205 · Cited by 236
Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders
Salvadores, N., Sanhueza, M., Manque, P., & Court, F. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00451 · Cited by 182
Revealing disease-associated pathways by network integration of untargeted metabolomics
Pirhaji, L., Milani, P., Leidl, M., Curran, T., Avila-Pacheco, J., Clish, C. B., White, F. M., Saghatelian, A., & Fraenkel, E. (2016) · Nature Methods · doi:10.1038/nmeth.3940 · Cited by 167
Self-citation
Metadata
- Authors
- Ng, C. W., Yildirim, F., Yap, Y. S., Dalin, S., Matthews, B. J., Velez, P. J., Labadorf, A., Housman, D. E., & Fraenkel, E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-01-22
- Volume
- 110
- Issue
- 6
- Pages
- 2354-2359
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2128077939
- Cited by
- 177
- References
- 7
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ng, C. W., Yildirim, F., Yap, Y. S., Dalin, S., Matthews, B. J., Velez, P. J., Labadorf, A., Housman, D. E., & Fraenkel, E. (2013). Extensive changes in DNA methylation are associated with expression of mutant huntingtin. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1221292110
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