Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex
Iris Cheung,Hennady P. Shulha,Yan Jiang,Anouch Matevossian,Jie Wang,Zhiping Weng,Zhiping Weng,Schahram Akbarian +7 more
TLDR
It is demonstrated that H3K4me3 in human PFC is highly regulated in a cell type- and subject-specific manner and the importance of early childhood for developmentally regulated chromatin remodeling in prefrontal neurons is highlighted.Abstract:
Little is known about the regulation of neuronal and other cell-type specific epigenomes from the brain. Here, we map the genome-wide distribution of trimethylated histone H3K4 (H3K4me3), a mark associated with transcriptional regulation, in neuronal and nonneuronal nuclei collected from prefrontal cortex (PFC) of 11 individuals ranging in age from 0.5 to 69 years. Massively parallel sequencing identified 12,732–19,704 H3K4me3 enriched regions (peaks), the majority located proximal to (within 2 kb of) the transcription start site (TSS) of annotated genes. These included peaks shared by neurons in comparison with three control (lymphocyte) cell types, as well as peaks specific to individual subjects. We identified 6,213 genes that show highly enriched H3K4me3 in neurons versus control. At least 1,370 loci, including annotated genes and novel transcripts, were selectively tagged with H3K4me3 in neuronal but not in nonneuronal PFC chromatin. Our results reveal age-correlated neuronal epigenome reorganization, including decreased H3K4me3 at approximately 600 genes (many function in developmental processes) during the first year after birth. In comparison, the epigenome of aging (>60 years) PFC neurons showed less extensive changes, including increased H3K4me3 at 100 genes. These findings demonstrate that H3K4me3 in human PFC is highly regulated in a cell type- and subject-specific manner and highlight the importance of early childhood for developmentally regulated chromatin remodeling in prefrontal neurons.read more
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Perinatal epigenetic determinants of cognitive and metabolic disorders.
TL;DR: This review will touch upon the Developmental Origins of Health and Disease (DoHAD) concept, while discussing recent advances in the understanding of metabolic and cognitive disruptions, with a focus on epigenetic factors, their transgenerational effects, and the consequences they might have upon the onset of chronic disease and premature exitus.
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Aging mechanisms—A perspective mostly from Drosophila
TL;DR: Current trends in aging research are discussed, various molecular markers implicated in aging are examined, and the use of Drosophila is highlighted, which allows controlled studies for evaluating genetic and environmental contributors to aging conveniently.
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Increased age is associated with epigenetic and structural changes in chromatin from neuronal nuclei.
Henrique F. Rodrigues,Tafarel Andrade de Souza,Flávia G. Ghiraldini,Maria Luiza S. Mello,Alberto S. Moraes +4 more
TL;DR: In this paper, the age-dependent relationship between structural and epigenetic alterations on chromatin of cortical neurons from mice was studied by image analysis after cytochemistry, or assessed for chromatin accessibility by enzymatic digestion.
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Neuron-Specific Menin Deletion Leads to Synaptic Dysfunction and Cognitive Impairment by Modulating p35 Expression
Kai Zhuang,Changquan Huang,Lige Leng,Honghua Zheng,Yuehong Gao,Guimiao Chen,Ji Zhilin,Hao Sun,Yu Hu,Di Wu,Meng Shi,Huifang Li,Yingjun Zhao,Yun-wu Zhang,Maoqiang Xue,Guojun Bu,Timothy Y. Huang,Huaxi Xu,Huaxi Xu,Jie Zhang +19 more
TL;DR: It is demonstrated that neuron-specific deletion of Men1 (CcKO) affects dendritic branching and spine formation, resulting in defects in synaptic function, learning, and memory, and it is found that menin binds to the p35 promoter region to facilitate p35 transcription.
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Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures.
TL;DR: The authors showed that ASH1L expression and H3K4me3 level are significantly decreased in the prefrontal cortex (PFC) of postmortem tissues from ASD patients, which indicated that Ash1L deficiency in PFC causes diminished GABAergic inhibition, enhanced glutamatergic transmission and elevated PFC pyramidal neuronal excitability, which is associated with severe seizures and early mortality.
References
More filters
Journal ArticleDOI
Gene Ontology: tool for the unification of biology
M Ashburner,Catherine A. Ball,Judith A. Blake,David Botstein,Heather Butler,J. M. Cherry,Allan Peter Davis,Kara Dolinski,Selina S. Dwight,J.T. Eppig,Midori A. Harris,David P. Hill,Laurie Issel-Tarver,Andrew Kasarskis,Suzanna E. Lewis,John C. Matese,Joel E. Richardson,M. Ringwald,Gerald M. Rubin,Gavin Sherlock +19 more
TL;DR: The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing.
Journal ArticleDOI
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome
TL;DR: Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches and can be used simultaneously to achieve even greater alignment speeds.
Journal ArticleDOI
Model-based Analysis of ChIP-Seq (MACS)
Yong Zhang,Tao Liu,Clifford A. Meyer,Jérôme Eeckhoute,David S. Johnson,Bradley E. Bernstein,Bradley E. Bernstein,Chad Nusbaum,Richard M. Myers,Myles Brown,Wei Li,X. Shirley Liu +11 more
TL;DR: This work presents Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer, and uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions.
Journal ArticleDOI
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Glynn Dennis,Brad T. Sherman,Douglas A. Hosack,Jun Jun Yang,Wei Gao,H. Clifford Lane,Richard A. Lempicki +6 more
TL;DR: DAMID is a web-accessible program that integrates functional genomic annotations with intuitive graphical summaries that assists in the interpretation of genome-scale datasets by facilitating the transition from data collection to biological meaning.
Journal ArticleDOI
High-resolution profiling of histone methylations in the human genome.
Artem Barski,Suresh Cuddapah,Kairong Cui,Tae-Young Roh,Dustin E. Schones,Zhibin Wang,Gang Wei,Iouri Chepelev,Keji Zhao +8 more
TL;DR: High-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology are generated.
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