5-hmC–mediated epigenetic dynamics during postnatal neurodevelopment and aging
By Keith E. Szulwach, Xuekun Li, Yujing Li, Chun-Xiao Song, Hao Wu, Qing Dai, Hasan A. Irier, A. Upadhyay, M. Gearing, A. Levey and 6 more. Nature Neuroscience, 2011
818 citations recorded by the source corpus.
DNA methylation dynamics influence brain function and are altered in neurological disorders. 5-hydroxymethylcytosine (5-hmC), a DNA base that is derived from 5-methylcytosine, accounts for ∼40% of modified cytosine in the brain and has been implicated in DNA methylation–related plasticity. We mapped 5-hmC genome-wide in mouse hippocampus and cerebellum at three different ages, which allowed us to assess its stability and dynamic regulation during postnatal neurodevelopment through adulthood. We found developmentally programmed acquisition of 5-hmC in neuronal cells. Epigenomic localization of 5-hmC–regulated regions revealed stable and dynamically modified loci during neurodevelopment and aging. By profiling 5-hmC in human cerebellum, we found conserved genomic features of 5-hmC. Finally, we found that 5-hmC levels were inversely correlated with methyl-CpG–binding protein 2 dosage, a protein encoded by a gene in which mutations cause Rett syndrome. These data suggest that 5-hmC–mediated epigenetic modification is critical in neurodevelopment and diseases.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/5a7e4af5b2f8a0e53deaaf8bf131b9ae8f6d97bd
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Citations in the corpus
- Measuring biological aging in humans: A quest (2019, background): “There is evidence that hydroxymethylation increases with aging in several brain regions, including the hippocampus, while declining in peripheral mononuclear cells (Szulwach et al., 2011, Valentini et al., 2016).”
- Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, neutral): “…be a hallmark of active transcription in virtually all cell-types investigated, including mouse/human ESCs (Ficz et al., 2011; Pastor et al., 2011; Szulwach et al., 2011a; Williams et al., 2011; Wu et al., 2011a; Xu et al., 2011b) (Rest in Figure 3B), mouse cerebellum (Mellén et al., 2012; Song…”
- Differential methylation analysis for BS-seq data under general experimental design (2016, background): “It often shows abnormality in many diseases such as cancer (Bird, 2002; Reik, 2007; Meissner et al., 2008; Kriaucionis and Heintz, 2009; Teschendorff et al., 2010; Szulwach et al., 2011b; Seisenberger et al., 2012).”
- Modification of enhancer chromatin: what, how and why? (2013, background): “…that 5mC undergoes enzymatic oxidation by the Tet family proteins to produce 5 hydroxymethyl-cytosine (5hmC), an intermediate on a pathway to active DNA demethylation via a couple of alterative biochemical pathways (reviewed in Dahl et al., 2011; Kriukien _e et al., 2012; Tan and Shi, 2012).”
- MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system (2013, neutral): “…example, 5hmC is present preferentially in specific classes of promoter and enhancer elements that regulate the pluripotent state in ES cells (Pastor et al., 2011; Yu et al., 2012; Booth at al., 2012), whereas in the brain it is enriched in gene bodies and depleted from TSS (Szulwach et al., 2011).”
- Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis (2014, background): “…during active demethylation of the DNA, especially TET1-mediated cytosine hydroxymethylation, gained interest as they seem to have regulatory function that differs from the simple absence of methylation (Kaas et al. 2013; Mellén et al. 2012 p. 2; Rudenko et al. 2013; Szulwach et al. 2011).”