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
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Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation
Xiaodong Zhu,David Girardo,Eve-Ellen Govek,Keisha John,Marian Mellén,Pablo Tamayo,Jill P. Mesirov,Mary E. Hatten +7 more
TL;DR: A role for Tet genes and chromatin remodeling genes in the formation of cerebellar circuitry is demonstrated using metagene analysis and it is demonstrated that Knockdown of Tet1 and Tet3 by RNAi in ex vivo cerebellary slice cultures inhibits dendritic arborization of developing GCs, a critical step in circuit formation.
Journal ArticleDOI
RNA sequencing and proteomics approaches reveal novel deficits in the cortex of Mecp2-deficient mice, a model for Rett syndrome.
Natasha L. Pacheco,Michael R. Heaven,Leanne M. Holt,Leanne M. Holt,David K. Crossman,Kristin J. Boggio,Scott A. Shaffer,Daniel Flint,Michelle L. Olsen,Michelle L. Olsen +9 more
TL;DR: This first comprehensive transcriptome-proteome comparison in a RTT mouse model is performed to elucidate RTT pathophysiology, identify potential therapeutic targets, and further the understanding of MeCP2 function.
Journal ArticleDOI
Interindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD
TL;DR: The potential application of epigenetic approaches in identifying markers of risk and resilience that can be utilized to promote early intervention and develop therapeutic strategies to combat PTSD after symptom onset are discussed.
Journal ArticleDOI
MECP2, a multi-talented modulator of chromatin architecture
Floriana Della Ragione,Marcella Vacca,Salvatore Fioriniello,Giuseppe Pepe,Maurizio D'Esposito +4 more
TL;DR: Even if the hunt for bona-fide MECP2 target genes is far from concluded today, the role of MeCP2 in the maintenance of chromatin architecture appears to be clearly established.
Journal ArticleDOI
MicroRNA-22 regulates smooth muscle cell differentiation from stem cells by targeting methyl CpG-binding protein 2.
Hanqing Zhao,Guanmei Wen,Yuan Huang,Xiaotian Yu,Qishan Chen,Tayyab Adeel Afzal,Le Anh Luong,Jianhua Zhu,Shu Ye,Li Zhang,Qingzhong Xiao +10 more
TL;DR: MiR-22 plays an important role in SMC differentiation, and epigenetic regulation through MECP2 is required for miR- 22 mediated SMC differentiated cells.
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