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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Journal ArticleDOI
DNA Methylation and Adult Neurogenesis.
Emily M. Jobe,Xinyu Zhao +1 more
TL;DR: Crosstalk between DNA methylation, Methyl-DNA binding domain (MBD) proteins such as MeCP2 and MBD1 and histone modifying complexes is used as an example to illustrate the extensive interconnection between these epigenetic regulatory systems.
Journal ArticleDOI
5-Hydroxymethylome in Circulating Cell-free DNA as A Potential Biomarker for Non-small-cell Lung Cancer.
Ji Zhang,Xiao Han,Chun-Chun Gao,Yurong Xing,Zheng Qi,Ruijuan Liu,Yueqin Wang,Xiaojian Zhang,Yun-Gui Yang,Xiangnan Li,Bao-Fa Sun,Xin Tian +11 more
TL;DR: The unique signature of 5hmC in tumor patient’s cfDNA identified in this study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.
Journal ArticleDOI
Altered hydroxymethylation is seen at regulatory regions in pancreatic cancer and regulates oncogenic pathways.
Sanchari Bhattacharyya,Kith Pradhan,Nathaniel R. Campbell,Jozef Mazdo,Aparna Vasantkumar,Shahina Maqbool,Tushar D. Bhagat,Sonal Gupta,Masako Suzuki,Yiting Yu,John M. Greally,Ulrich Steidl,James E. Bradner,Meelad M. Dawlaty,Lucy A. Godley,Anirban Maitra,Amit Verma +16 more
TL;DR: Red redistribution of 5-hmC and preferential enrichment at oncogenic enhancers is a novel regulatory mechanism in human pancreatic cancer.
Journal ArticleDOI
Genome-wide alteration in DNA hydroxymethylation in the sperm from bisphenol A-exposed men.
Huajun Zheng,Xiaoyu Zhou,De-Kun Li,Fen Yang,Hongjie Pan,Tianqi Li,Maohua Miao,Runsheng Li,Wei Yuan +8 more
TL;DR: BPA exposure likely interferes with gene expression via affecting DNA hydroxymethylation in a way partially dependent on trimethylation of H3 in human spermatogenesis, a new mechanism by which BPA exposure reduces human sperm quality.
Journal ArticleDOI
Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals.
Jeffrey A. Gross,Alain Pacis,Gary Gang Chen,Drupals M,Pierre-Eric Lutz,Luis B. Barreiro,Gustavo Turecki +6 more
TL;DR: The results present a novel mechanism linking increased 5hmC to depression and provide a framework for future research in this field, as well as validated CpGs in the gene body of myosin XVI and insulin-degrading enzyme using targeted oxidative bisulfite sequencing.
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