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
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Dissertation
The role of chromatin organization and structure in neuronal differentiation
TL;DR: A complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line and the role of chromatin structure and organization on neural differentiation and stem cell maintenance is studied.
The Role of Schwann Cell Mitochondrial Metabolism in Schwann Cell Biology and Axonal Survival
TL;DR: Using nanofiltration membranes for the recovery of phosphorous with a second type of technology for the separation of nitrogen and carbon dioxide is suggest to be a viable process.
Inflammation Alters Histone Methylation in the Central Nervous System: Implications for Neuropsychiatric Disease: A Dissertation
TL;DR: The focus of this thesis was to examine the effect of inflammation on the histone modification, trimethylated histone H3 lysine 4 (H3K4me3), which has been implicated in both normal brain development and in schizophrenia.
Book ChapterDOI
Epigenetic Regulation in Autism
TL;DR: This chapter discusses matters of epigenetic heritability as it pertains to autism spectrum disorders, highlight monogenic forms of the disorder associated with disordered chromatin structure and function, and summarizes the current knowledge base as itpertains to epigenetic regulation during normal aging and development.
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