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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Transcriptional and epigenetic mechanisms of addiction
TL;DR: Multiple mechanisms by which drugs alter the transcriptional potential of genes are reviewed, including alterations in the accessibility of genes within their native chromatin structure induced by histone tail modifications and DNA methylation, and the regulation of gene expression by non-coding RNAs.
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Common genetic variants influence human subcortical brain structures.
Derrek P. Hibar,Jason L. Stein,Jason L. Stein,Miguel E. Rentería,Alejandro Arias-Vasquez,Sylvane Desrivières,Neda Jahanshad,Roberto Toro,Roberto Toro,Katharina Wittfeld,Katharina Wittfeld,Lucija Abramovic,Micael Andersson,Benjamin S. Aribisala,Benjamin S. Aribisala,Nicola J. Armstrong,Nicola J. Armstrong,Manon Bernard,Marc M. Bohlken,Marco P. Boks,Janita Bralten,Andrew A. Brown,M. Mallar Chakravarty,M. Mallar Chakravarty,Qiang Chen,Christopher R.K. Ching,Christopher R.K. Ching,Gabriel Cuellar-Partida,Anouk den Braber,Sudheer Giddaluru,Aaron Goldman,Oliver Grimm,Tulio Guadalupe,Johanna Hass,Girma Woldehawariat,Avram J. Holmes,Avram J. Holmes,Martine Hoogman,Deborah Janowitz,Tianye Jia,Sungeun Kim,Marieke Klein,Bernd Kraemer,Phil Lee,Phil Lee,Loes M. Olde Loohuis,Michelle Luciano,Christine Macare,Karen A. Mather,Manuel Mattheisen,Manuel Mattheisen,Yuri Milaneschi,Kwangsik Nho,Martina Papmeyer,Adaikalavan Ramasamy,Adaikalavan Ramasamy,Shannon L. Risacher,Roberto Roiz-Santiañez,Emma J. 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The Cellular and Molecular Landscapes of the Developing Human Central Nervous System.
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Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development.
Stefan Bonn,Robert P. Zinzen,Charles Girardot,E. Hilary Gustafson,Alexis Perez-Gonzalez,Nicolas Delhomme,Yad Ghavi-Helm,Bartek Wilczyński,Andrew Riddell,Eileen E. M. Furlong +9 more
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