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
Citations
More filters
Journal ArticleDOI
Transcriptional Enhancers in the FOXP2 Locus Underwent Accelerated Evolution in the Human Lineage.
TL;DR: The results indicate that regulatory sequences in the FOXP2 locus underwent a human-specific evolutionary process suggesting that the transcriptional machinery controlling this gene could have also evolved differentially in the human lineage.
Journal ArticleDOI
Chromatin Architecture and the Regulation of Nuclear Receptor Inducible Transcription
Simon C. Biddie,Simon C. Biddie +1 more
TL;DR: The current knowledge of the mechanisms regulating nuclear receptor occupancy at cis‐regulatory elements is discussed, with particular emphasis on the glucocorticoid, oestrogen and androgen receptors.
Journal ArticleDOI
Blood chromatin as a biosensor of the epigenetic milieu: a tool for studies in living psychiatric patients.
TL;DR: An argument for using blood chromatin (contained in nucleated blood cells) as a protein biosensor to integrate the ambient epigenetic influences in the internal milieu is constructed.
Posted ContentDOI
Evaluation Of Chromatin Accessibility In Prefrontal Cortex Of Schizophrenia Cases And Controls
Julien Bryois,Melanie E. Garrett,Lingyun Song,Alexias Safi,Paola Giusti-Rodríguez,Graham Johnson,Alfonso Buil Demur,John F. Fullard,Panos Roussos,Pamela Sklar,Schahram Akbarian,Vahram Haroutunian,Craig A. Stockmeier,Gregory A. Wray,Kevin P. White,Chunyu Liu,Timothy E. Reddy,Allison E. Ashley-Koch,Patrick F. Sullivan,Gregory E. Crawford +19 more
TL;DR: The results strongly implicate gene regulatory processes involving open chromatin in the pathogenesis of schizophrenia, and suggest a strategy to understand the hundreds of common variants emerging from large genomic studies of complex brain diseases.
Book ChapterDOI
The future of neuroepigenetics in the human brain.
TL;DR: It is proposed that comprehensive, cell type-specific mappings of DNA and histone modifications, chromatin-associated RNAs, and chromosomal "loopings" and other determinants of three-dimensional genome organization will critically advance insight into the pathophysiology of the disease.
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.
Related Papers (5)
Global Epigenomic Reconfiguration During Mammalian Brain Development
Ryan Lister,Ryan Lister,Eran A. Mukamel,Joseph R. Nery,Mark A. Urich,Clare A. Puddifoot,Nicholas D. Johnson,Jacinta Lucero,Yun Huang,Andrew J. Dwork,Matthew D. Schultz,Matthew D. Schultz,Miao Yu,Julian Tonti-Filippini,Holger Heyn,Shijun Hu,Joseph C. Wu,Anjana Rao,Manel Esteller,Chuan He,Fatemeh Haghighi,Terrence J. Sejnowski,Terrence J. Sejnowski,M. Margarita Behrens,Joseph R. Ecker +24 more