Genome-wide incorporation dynamics reveal distinct categories of turnover for the histone variant H3.3
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE51505 | GEO | 2013/10/23
SECONDARY ACCESSION(S): PRJNA223387
REPOSITORIES: GEO
Similar Datasets
Project description:We developed a system to study the DNA replication-independent turnover nucleosomes containing the histone variant H3.3 in mammalian cells. By measuring the genome-wide incorporation of H3.3 at different time points following epitope-tagged H3.3 expression, we find three categories of H3.3-nucleosome turnover in vivo: rapid turnover, intermediate turnover and, specifically at telomeres, slow turnover. Our data indicate that H3.3-containing nucleosomes at enhancers and promoters undergo a rapid turnover that is associated with active histone modification marks including H3K4me1, H3K4me3, H3K9ac, H3K27ac and the histone variant H2A.Z. The rate of turnover is negatively correlated with H3K27me3 at regulatory regions and with H3K36me3 at gene bodies. Examination of incorporation dynamics of histone variant H3.3
2013-10-23 | E-GEOD-51505 | biostudies-arrayexpress
Project description:Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3 containing nucleosomes remain highly dynamic–in a modification independent manner–to control neuronal- and glial- specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical, and previously undocumented, regulator of cell-type specific transcription and plasticity in mammalian brain. All RNA-seq samples were generated to test the impact of neuronal activity/adult physiological plasticity on histone turnover turnover mediated alterations in mRNA expression in the central nervous system. This was tested in cultured neurons and astrocytes, and embryonic/adult brain tissues
2015-06-23 | E-GEOD-69807 | biostudies-arrayexpress
Project description:Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3 containing nucleosomes remain highly dynamic–in a modification independent manner–to control neuronal- and glial- specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical, and previously undocumented, regulator of cell-type specific transcription and plasticity in mammalian brain. All ChIP-seq samples were generated to test the impact of neuronal activity/adult physiological plasticity on histone turnover in the central nervous system. This was tested in cultured neurons and astrocytes, FACS purified neurons or FACS purified Glia.
2015-06-23 | E-GEOD-69806 | biostudies-arrayexpress
Project description:Histone H3 is assembled into nucleosomes during replication but is replaced by the H3.3 variant at sites of active transcription. Thus replacement levels provide a quantitative measure of histone turnover during transcriptional elongation and other active processes in dividing cells. Here we provide new insights into epigenetic regulation with the first genome-wide chromatin profile at 100-bp resolution, based on measurements of H3.3 levels throughout the Drosophila genome. These data are unpublished. Keywords: Chromatin affinity-purification on microarray
2007-12-01 | GSE4091 | GEO
Project description:Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3 containing nucleosomes remain highly dynamic–in a modification independent manner–to control neuronal- and glial- specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical, and previously undocumented, regulator of cell-type specific transcription and plasticity in mammalian brain.
2015-06-23 | GSE69806 | GEO
Project description:Turnover and exchange of nucleosomal histones and their variants, a process long believed to be static in post-replicative cells, remains largely unexplored in brain. Here, we describe a novel mechanistic role for HIRA (histone cell cycle regulator) and proteasomal degradation associated histone dynamics in the regulation of activity-dependent transcription, synaptic connectivity and behavior. We uncover a dramatic developmental profile of nucleosome occupancy across the lifespan of both rodents and humans, with the histone variant H3.3 accumulating to near saturating levels throughout the neuronal genome by mid-adolescence. Despite such accumulation, H3.3 containing nucleosomes remain highly dynamic–in a modification independent manner–to control neuronal- and glial- specific gene expression patterns throughout life. Manipulating H3.3 dynamics in both embryonic and adult neurons confirmed its essential role in neuronal plasticity and cognition. Our findings establish histone turnover as a critical, and previously undocumented, regulator of cell-type specific transcription and plasticity in mammalian brain.
2015-06-23 | GSE69807 | GEO
Project description:Nucleosome turnover concomitant with incorporation of the replication-independent histone variant H3.3 is a hallmark of regulatory regions in the animal genome. In our current understanding, nucleosome turnover is universally linked to DNA accessibility and histone acetylation. In mouse embryonic stem cells, H3.3 is also highly enriched at interstitial heterochromatin, most prominently intracisternal-A particle endogenous retroviral elements. Interstitial heterochromatin is established over confined domains by the TRIM28/SETDB1 corepressor complex and has stereotypical features of repressive chromatin, such as H3K9me3 and recruitment of all HP1 isoforms. Here, we demonstrate that fast histone turnover and H3.3 incorporation is compatible with these hallmarks of heterochromatin. We identify Smarcad1 to be a chromatin remodeler that generates nucleosome-free regions which are subsequently filled with histone H3.3, generating a surprisingly dynamic heterochromatin state. Loss of histone H3.3 elicits a highly specific opening of interstitial heterochromatin demonstrating that in the wake of Smarcad1 remodeling, H3.3 is required to maintain minimal DNA accessibility by reassembling nucleosomes.
2020-08-28 | GSE149080 | GEO
Project description:Direct measurement of nucleosome turnover dynamics by using co-translational incorporation of the methionine (Met) surrogate azidohomoalaine (Aha) into proteins and subsequent ligation of biotin to Aha-containing proteins through the [3+2] cycloaddition reaction between the azide group of Aha and an alkyne linked to biotin. To measure turnover rates, we treat cells briefly with Aha, couple biotin to nucleosomes containing newly incorporated histones, affinity purify with strepavidin, wash stringently to remove non-histone proteins and H2A/H2B dimers, and analyze the affinity-purified DNA using tiling microarrays. We call this strategy 'CATCH-IT' for Covalent Attachment of Tags to Capture Histones and Identify Turnover. Keywords: Chromatin affinity-purification on microarray All experiments were done using strepavidin pulldown DNA cohybridized with total input DNA to the same array. Two channels per array, Cy5 and Cy3, were used in each experiment.
2010-05-27 | E-GEOD-19788 | biostudies-arrayexpress
Project description:Nucleosomes are the principal packaging units of chromatin and critical for gene regulation and genome stability. In mammals, a subset of nucleosomes fail to be replaced by protamines during spermatogenesis and are retained in mature spermatozoa providing opportunities for paternal epigenetic transmission. In humans, the remaining 10% localize at regulatory elements of genes. To assess evolutionary conservation and to dissect the molecular logic underlying nucleosome retention, we determined the genome wide nucleosome occupancy in mouse spermatozoa that only contain 1% residual histones. In striking contrast to mammalian somatic cells and haploid round spermatids, we observe high enrichment of nucleosomes at CpG-rich sequences throughout the genome, at conserved regulatory sequences as well as at intra- and intergenic regions and repetitive DNA. This preferred occupancy occurs mutually exclusive with DNA methylation both in mouse and human sperm. At unmethylated CpG-rich sequences, residing nucleosomes are largely composed of the H3.3 histone variant, and trimethylated at lysine 4 (H3K4me3). Both canonical H3.1/H3.2 and H3.3 variant histones are present at promoters marked by Polycomb-mediated H3K27me3, which is strongly predictive for gene repression in pre-implantation embryos. Our data indicate important roles of DNA sequence composition, DNA methylation, variant H3.3 and canonical H3.1/H3.2 histones and associated modifications in nucleosome retention versus eviction during the histone-to-protamine remodeling process in elongating spermatids and potentially in epigenetic inheritance by nucleosomes between generations. Identification of histone, histone variant and histone modification states in round spermatids and sperm
2013-06-15 | E-GEOD-42629 | biostudies-arrayexpress
Project description:Direct measurement of nucleosome turnover dynamics by using co-translational incorporation of the methionine (Met) surrogate azidohomoalaine (Aha) into proteins and subsequent ligation of biotin to Aha-containing proteins through the [3+2] cycloaddition reaction between the azide group of Aha and an alkyne linked to biotin. To measure turnover rates, we treat cells briefly with Aha, couple biotin to nucleosomes containing newly incorporated histones, affinity purify with strepavidin, wash stringently to remove non-histone proteins and H2A/H2B dimers, and analyze the affinity-purified DNA using tiling microarrays. We call this strategy 'CATCH-IT' for Covalent Attachment of Tags to Capture Histones and Identify Turnover. Keywords: Chromatin affinity-purification on microarray
2010-05-27 | GSE19788 | GEO