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Deciphering H3K4me3 Broad Domains Associated With Gene Regulatory Networks and Conserved Epigenomic Landscapes in the Human Brain [ChIP-Seq]

ABSTRACT: Trimethylated histone H3-lysine 4 is primarily distributed in the form of sharp peaks, extending in neuronal chromatin on average only across 500-1500 base pairs mostly in close proximity to annotated transcription start sites. To explore whether H3K4me3 peaks could also extend across much broader domains, we undertook a detailed analysis of broadest domain cell-type specific H3K4me3 peaks in ChIP-seq datasets from sorted neuronal and non-neuronal nuclei in human, non-human primate and mouse prefrontal cortex (PFC), and blood for comparison. In this GEO submission, we list six newly generated ChIP-seq data sets. FACS sorted Neuronal (NeuN+) nuclei and non-neuronal (NeuN-) nuclei collected from prefrontal cortex (PFC) and processed by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq). In addition we collected nucleated blood cells from 3 control subjects. These are additional subjects unrelated to brain cohort.

ORGANISM(S): Homo sapiens

SUBMITTER: Aslihan Dincer

PROVIDER: E-GEOD-72929 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Deciphering H3K4me3 Broad Domains Associated With Gene Regulatory Networks and Conserved Epigenomic Landscapes in the Human Brain [RNA-Seq]

Project description:Trimethylated histone H3-lysine 4 is primarily distributed in the form of sharp peaks, extending in neuronal chromatin on average only across 500-1500 base pairs mostly in close proximity to annotated transcription start sites. To explore whether H3K4me3 peaks could also extend across much broader domains, we undertook a detailed analysis of broadest domain cell-type specific H3K4me3 peaks in ChIP-seq datasets from sorted neuronal and non-neuronal nuclei in human, non-human primate and mouse prefrontal cortex (PFC), and blood for comparison. We collected separately cortical gray (GM) and subcortical white matter (WM) from 6 adult human subjects without neurological disease and extracted total RNA processed by the RNA-Seq approach.

2016-07-21 | E-GEOD-72930 | biostudies-arrayexpress

Developmental Regulation and Individual Differences of Neuronal Epigenomes in the Prefrontal Cortex

Project description:We report global distribution of trimethylated Histone H3 Lysine 4 (H3K4me3) in human prefrontal cortex neurons at different ages Neuronal nuclei from human prefrontal cortex were isolated by FACS. Regions marked by H3K4me3 were identified by chromatin immunoprecipiation followed by deep sequencing.

2010-04-20 | E-GEOD-21172 | biostudies-arrayexpress

Deciphering H3K4me3 Broad Domains Associated With Gene Regulatory Networks and Conserved Epigenomic Landscapes in the Human Brain [RNA-Seq]

2016-07-21 | GSE72930 | GEO

Deciphering H3K4me3 Broad Domains Associated With Gene Regulatory Networks and Conserved Epigenomic Landscapes in the Human Brain [ChIP-Seq]

Project description:Trimethylated histone H3-lysine 4 is primarily distributed in the form of sharp peaks, extending in neuronal chromatin on average only across 500-1500 base pairs mostly in close proximity to annotated transcription start sites. To explore whether H3K4me3 peaks could also extend across much broader domains, we undertook a detailed analysis of broadest domain cell-type specific H3K4me3 peaks in ChIP-seq datasets from sorted neuronal and non-neuronal nuclei in human, non-human primate and mouse prefrontal cortex (PFC), and blood for comparison. In this GEO submission, we list six newly generated ChIP-seq data sets.

2016-07-21 | GSE72929 | GEO

Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability [ATAC-Seq]

Project description:We analyzed differential methylation (via WGBS) between four distinct human brain regions (NAcc-nucleus accumbens, BA9-dorsolateral prefrontal cortex, BA24-anterior cingulate cortex, and HC-hippocampus) in both sorted nuclei and intact tissues. We isolated neuronal and non-neuronal (glial) nuclei from the same six individuals for each tissue via FACS using the neuronal marker, NeuN. Additionally, we performed WGBS from non-sorted tissues from these same brain regions in a total of 12 individuals (BA9 n = 9; BA24 n = 5; HC n = 6; NAcc n = 7). To complement our DNA methylation analyses, we measured gene expression (RNA-seq) and chromatin accessibility (ATAC-seq) in neuronal and non-neuronal nuclei from the nucleus accumbens and dorsolateral prefrontal cortex from six more individuals. We then performed an integrative analysis to understand how the epigenome contributes to brain region-specific function.

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Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability [RNA-Seq]

2018-12-17 | GSE96613 | GEO

Neuronal brain region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability [Bisulfite-Seq]

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H3K4me3 modification profiling of Huntingtons disease and control human post-mortem prefrontal cortex brain samples

Project description:Huntingtonâs disease (HD) is an autosomal-dominant neurodegenerative disorder resulting from expansion in the number of CAG repeats in the coding region of exon 1 of the Huntingtin (HTT) gene. One of the most widely studied chromatin modifications is trimethylated lysine 4 of histone 3 (H3K4me3). Here, we conducted the first comprehensive study of H3K4me3 ChIP-sequencing in neuronal chromatin from the prefrontal cortex of six HD cases and six non-neurologic controls. We examined two classes of H3K4me3 peaks; those located near transcription start sites (TSSs) (termed âproximalâ) and those located distantly from TSSs (termed âdistalâ). We detected 2,830 differentially enriched H3K4me3 peaks between HD and controls, with 55% of them down regulated in HD. We found an unexpected discordance between levels of H3K4me3 and mRNA, with H3K4me3 predominantly reduced in HD and mRNA predominantly increased in HD. Gene ontology (GO) term enrichment analysis of the genes associated with the proximally positioned peaks, revealed diverse biological process terms with organ morphogenesis and positive regulation of gene expression most frequently implicated. GO terms relating to transcription and the extracellular matrix were also observed. Approximately 36% of the distal peaks co-localized to enhancer sites, with six transcription factors and chromatin remodelers differentially enriched in HD H3K4me3 distal peaks, including EZH2 and SUZ12, two core subunits of the polycomb repressive complex 2 (PRC2). Moreover, sequences repressed by polycomb in normal frontal cortex were significantly depleted in HD-enriched peaks, suggesting that H3K4me3 histone hypermethylation is linked to dysregulated polycomb activity in the HD neuronal epigenome. 12 H3K4me3 ChIP-seq libraries (6 Huntington's disease, 6 neurologically normal control), and 1 input DNA library (neurologically normal control)

2015-12-14 | E-GEOD-68952 | biostudies-arrayexpress

Neuronal Kmt2a/Mll1 histone methyltransferase is essential for prefrontal synaptic plasticity and working memory

Project description:Neuronal histone H3-lysine 4 methylation landscapes are defined by sharp peaks at gene promoters and other cis-regulatory sequences, but molecular and cellular phenotypes after neuron-specific deletion of H3K4 methyl-regulators remain largely unexplored. We report that neuronal ablation of the H3K4-specific methyltransferase, Kmt2a/Mixed-lineage leukemia 1 (Mll1), in mouse postnatal forebrain and adult prefrontal cortex (PFC) is associated with increased anxiety and robust cognitive deficits without locomotor dysfunction. In contrast, only mild behavioral phenotypes were observed after ablation of the Mll1 ortholog Kmt2b/Mll2 in PFC. Impaired working memory after Kmt2a/Mll1 ablation in PFC neurons was associated with loss of training-induced transient waves of Arc immediate early gene expression critical for synaptic plasticity. Medial prefrontal layer V pyramidal neurons, a major output relay of the cortex, demonstrated severely impaired synaptic facilitation and temporal summation, two forms of short-term plasticity essential for working memory. Chromatin immunoprecipitation followed by deep sequencing in Mll1-deficient cortical neurons revealed downregulated expression and loss of the transcriptional mark, trimethyl-H3K4, at <50 loci, including the homeodomain transcription factor Meis2. Small RNA-mediated Meis2 knockdown in PFC was associated with working memory defects similar to those elicited by Mll1 deletion. Therefore, mature prefrontal neurons critically depend on maintenance of Mll1-regulated H3K4 methylation at a subset of genes with an essential role in cognition and emotion.

2016-10-06 | GSE87675 | GEO

Conserved expression of lincRNA during human and macaque prefrontal cortex development and maturation

Project description:78 tissue samples from prefrontal cortex (PFC) in human and macaque The data from human and macaque PFC samples with different ages were used to estimate gene expression changes, including both protein-coding genes and lincRNAs, in PFC along lifespan in the two species.

2014-05-14 | E-GEOD-51264 | biostudies-arrayexpress

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