The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders.
TLDR
This mini-review covers the current knowledge on the regulatory mechanisms controlling in particular DNA demethylation as well as the possible functional consequences in health and disease.Abstract:
Over the last decade, an increasing number of reports underscored the importance of epigenetic regulations in brain plasticity. Epigenetic elements such as readers, writers, and erasers recognize, establish, and remove the epigenetic tags in nucleosomes, respectively. One such regulation concerns DNA-methylation and demethylation, which are highly dynamic and activity-dependent processes even in the adult neurons. It is nowadays widely believed that external stimuli control the methylation marks on the DNA and that such processes serve transcriptional regulation in neurons. In this mini-review, we cover the current knowledge on the regulatory mechanisms controlling in particular DNA demethylation as well as the possible functional consequences in health and disease.read more
Citations
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Journal ArticleDOI
Single-Cell Multi-omic Integration Compares and Contrasts Features of Brain Cell Identity.
Joshua D. Welch,Velina Kozareva,Ashley Ferreira,Charles R. Vanderburg,Carly A. Martin,Evan Z. Macosko,Evan Z. Macosko +6 more
TL;DR: LIGER, an algorithm that delineates shared and dataset-specific features of cell identity, was applied to four diverse and challenging analyses of human and mouse brain cells, revealing putative mechanisms of cell-type-specific epigenomic regulation.
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Specific expression of activation-induced cytidine deaminase (AID) , a novel member of the RNA editing deaminase family in germinal center B cells
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Mitochondrial DNA: Epigenetics and environment.
TL;DR: An overview of the epigenetic regulation of mtDNA via methylation, long and short noncoding RNAs, and post‐translational modifications of nucleoid proteins (as mitochondria lack histones) is provided.
Journal ArticleDOI
Estradiol-Induced Epigenetically Mediated Mechanisms and Regulation of Gene Expression.
TL;DR: The basic mechanisms and interactions between estrogen receptors and DNA methylation, demethylation and histone modification processes as well as chromatin remodeling complexes are surveyed.
Posted ContentDOI
Integrative inference of brain cell similarities and differences from single-cell genomics
Joshua D. Welch,Kozareva,Ferreira A,Charles R. Vanderburg,Caroline Martin,Evan Z. Macosko,Evan Z. Macosko +6 more
TL;DR: LIGER, an algorithm that delineates shared and dataset-specific features of cell identity, allowing flexible modeling of highly heterogeneous single-cell datasets, is developed and demonstrated its broad utility by applying it to four diverse and challenging analyses of human and mouse brain cells.
References
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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
Functions of DNA methylation: islands, start sites, gene bodies and beyond
TL;DR: Improved genome-scale mapping of methylation allows us to evaluate DNA methylation in different genomic contexts: transcriptional start sites with or without CpG islands, in gene bodies, at regulatory elements and at repeat sequences.
Journal ArticleDOI
Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine
Shinsuke Ito,Li Shen,Qing Dai,Susan C. Wu,Leonard B. Collins,James A. Swenberg,Chuan He,Yi Zhang +7 more
TL;DR: This study raises the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation, and identifies two previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins.
Journal ArticleDOI
The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
TL;DR: It is shown that, as well as 5mC in mammalian genomes, there are also significant amounts of 5-hydroxymethylcytosine (5hmC) in DNA of Purkinje neurons, which have large nuclei with apparently very little heterochromatin.
Journal ArticleDOI
Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA
Yu-Fei He,Bin-Zhong Li,Zheng Li,Peng Liu,Yang Wang,Qingyu Tang,Jianping Ding,Yingying Jia,Zhangcheng Chen,Lin Li,Yan Sun,Xiuxue Li,Qing Dai,Chun-Xiao Song,Kangling Zhang,Chuan He,Guoliang Xu +16 more
TL;DR: It is demonstrated that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells, suggesting that oxidation of 5m C by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.