MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
TLDR
In this paper, a quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo is presented.Abstract:
SUMMARY The high level of 5-hydroxymethylcytosine (5hmC) present in neuronal genomes suggests that mechanisms interpreting 5hmC in the CNS may differ from those present in embryonic stem cells. Here, we present quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo. We report that 5hmC is enriched in active genes and that, surprisingly, strong depletion of 5mC is observed over these regions. The contribution of these epigenetic marks to gene expression depends critically on cell type. We identify methyl-CpG-binding protein 2 (MeCP2) as the major 5hmC-binding protein in the brain and demonstrate that MeCP2 binds 5hmC- and 5mC-containing DNA with similar high affinities. The Rett-syndrome-causing mutation R133C preferentially inhibits 5hmC binding. These findings support a model in which 5hmC and MeCP2 constitute a cell-specific epigenetic mechanism for regulation of chromatin structure and gene expression.read more
Citations
More filters
Journal ArticleDOI
Gene regulation and genetics in neurochemistry, past to future.
TL;DR: Expanding these considerations to non‐peptide neurotransmitters illustrates how gene regulatory events impact neurochemistry in a much broader sense, extending beyond the neurochemicals that translate electrical signals into chemical ones in the synapse, to also include every aspect of neural development, structure, function, and pathology.
Journal ArticleDOI
DNA methylation and hydroxymethylation characterize the identity of D1 and D2 striatal projection neurons
Lucile Marion-Poll,Jean-Pierre Roussarie,Lieng Taing,Cloelia Dard-Dascot,Nicolas Servant,Yan Jaszczyszyn,Emmanuelle Jordi,Eskeatnaf Mulugeta,Denis Hervé,Déborah Bourc'his,Paul Greengard,Claude Thermes,Jean-Antoine Girault +12 more
TL;DR: In this article , the authors compare translating mRNAs and DNA modifications in striatal projection neurons expressing D1 or D2 dopamine receptors and reveal epigenetic characteristics of neuronal DNA modifications.
Dissertation
Epigenetic mechanisms underlying seasonal timing in Nasonia vitripennis
TL;DR: In this article, the role of epigenetics in the photoperiodic response of the Nasonia vitripennis was investigated and the results showed that 5-hydroxy methyl cytosine (5hmC) is an intermediate in DNA demethylation in mammals.
Journal ArticleDOI
Selective modulation of local linkages between active transcription and oxidative demethylation activity shapes cardiomyocyte-specific gene-body epigenetic status in mice.
Mayumi Oda,Shunichi Wakabayashi,N. Ari Wijetunga,Shinsuke Yuasa,Hirokazu Enomoto,Ruri Kaneda,Sung Han Yoon,Nishant Mittal,Qiang Jing,Masako Suzuki,John M. Greally,Keiichi Fukuda,Shinji Makino +12 more
TL;DR: Demethylation in CMs can be a used to establish such cell-type-specific epigenetic domains in relation to liver cells, and may contribute to the development of cell- type-specific transcriptional coordination.
Journal ArticleDOI
Epigenetics: Integrating Genetic Programs, Brain Development and Emergent Phenotypes
TL;DR: A review of recent developments revealing epigenetic aspects of mental illness, as well as review some of the challenges of current approaches and some future directions in the field of behavioral epigenetics can be found in this paper.
References
More filters
Journal ArticleDOI
Differential expression analysis for sequence count data.
Simon Anders,Wolfgang Huber +1 more
TL;DR: A method based on the negative binomial distribution, with variance and mean linked by local regression, is proposed and an implementation, DESeq, as an R/Bioconductor package is presented.
Journal ArticleDOI
Mapping and quantifying mammalian transcriptomes by RNA-Seq.
TL;DR: Although >90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3′ untranscribed regions, as well as new candidate microRNA precursors.
Journal ArticleDOI
Bioconductor: open software development for computational biology and bioinformatics
Robert Gentleman,Vincent J. Carey,Douglas M. Bates,Benjamin M. Bolstad,Marcel Dettling,Sandrine Dudoit,Byron Ellis,Laurent Gautier,Yongchao Ge,Jeff Gentry,Kurt Hornik,Torsten Hothorn,Wolfgang Huber,Stefano Maria Iacus,Rafael A. Irizarry,Friedrich Leisch,Cheng Li,Martin Maechler,A. J. Rossini,Günther Sawitzki,Colin A. Smith,Gordon K. Smyth,Luke Tierney,Jean Yang,Jianhua Zhang +24 more
TL;DR: Details of the aims and methods of Bioconductor, the collaborative creation of extensible software for computational biology and bioinformatics, and current challenges are described.
Journal ArticleDOI
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Mamta Tahiliani,Kian Peng Koh,Yinghua Shen,William A. Pastor,Hozefa S. Bandukwala,Yevgeny Brudno,Suneet Agarwal,Lakshminarayan M. Iyer,David R. Liu,L. Aravind,Anjana Rao +10 more
TL;DR: It is shown here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro.
Journal ArticleDOI
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
Ruthie E. Amir,Ignatia B. Van den Veyver,Mimi Wan,Charles Q. Tran,Uta Francke,Huda Y. Zoghbi +5 more
TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.