The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
α-Synuclein Sequesters Dnmt1 from the Nucleus
Open accessAbstract
DNA methylation is a major epigenetic modification that regulates gene expression. Dnmt1, the maintenance DNA methylation enzyme, is abundantly expressed in the adult brain and is mainly located in the nuclear compartment, where it has access to chromatin. Hypomethylation of CpG islands at intron 1 of the SNCA gene has recently been reported to result in overexpression of α-synuclein in Parkinson disease (PD) and related disorders. We therefore investigated the mechanisms underlying altered DNA methylation in PD and dementia with Lewy bodies (DLB). We present evidence of reduction of nuclear Dnmt1 levels in human postmortem brain samples from PD and DLB patients as well as in the brains of α-synuclein transgenic mice models. Furthermore, sequestration of Dnmt1 in the cytoplasm results in global DNA hypomethylation in human and mouse brains, involving CpG islands upstream of SNCA, SEPW1, and PRKAR2A genes. We report that association of Dnmt1 and α-synuclein might mediate aberrant subcellular localization of Dnmt1. Nuclear Dnmt1 levels were partially rescued by overexpression of Dnmt1 in neuronal cell cultures and in α-synuclein transgenic mice brains. Our results underscore a novel mechanism for epigenetic dysregulation in Lewy body diseases, which might underlie the decrease in DNA methylation reported for PD and DLB.
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Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382
Spencer, B., Potkar, R., Trejo, M., Rockenstein, E., Patrick, C., Gindi, R., Adame, A., Wyss-Coray, T., & Masliah, E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.4390-09.2009 · Cited by 595
Self-citationRockenstein, E., Mallory, M., Hashimoto, M., Song, D., Shults, C. W., Lang, I., & Masliah, E. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10231 · Cited by 502
Self-citation
Cited by
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
Epigenetic mechanisms in neurological disease
Jakovcevski, M., & Akbarian, S. (2012) · Nature Medicine · doi:10.1038/nm.2828 · Cited by 450
CpG and non-CpG methylation in epigenetic gene regulation and brain function
Jang, H., Shin, W., Lee, J., & Do, J. (2017) · Genes · doi:10.3390/genes8060148 · Cited by 427
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
One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration
Lionaki, E., Ploumi, C., & Tavernarakis, N. (2022) · Cells · doi:10.3390/cells11020214 · Cited by 110
Metadata
- Authors
- Desplats, P., Spencer, B., Coffee, E., Patel, P., Michael, S., Patrick, C., Adame, A., Rockenstein, E., & Masliah, E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 286
- Issue
- 11
- Pages
- 9031-9037
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2090999212
- Cited by
- 305
- References
- 3
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
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