Age- and cell type- specific effects of histone variant H2BE in the brain
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Sean Louzon
PROVIDER: PXD069021 | panorama | Sun Nov 09 00:00:00 GMT 2025
REPOSITORIES: PanoramaPublic
Similar Datasets
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:We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. The objective of generating this dataset was to analyze the occupancy of H2BE protein in the vicinity of gene promoters throughout the genome, relative to histone H3, in olfactory sensory neurons within the main olfactory epithelium (MOE). This dataset analyzes the occupancy of FLAG-H2BE protein in the vicinity of gene promoters throughout the genome, relative to histone H3, in olfactory sensory neurons within the main olfactory epithelium (MOE) of Flag-H2be transgenic mice, which express a FLAG-tagged version of H2BE from the H2be promoter. There are 2 replicates for each ChIP (FLAG and H3).
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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
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Project description:A cell’s ability to respond and adapt to environmental stimuli relies in part on transcriptional programs controlled by histone proteins. Histones affect transcription through numerous mechanisms including through replacement with variant forms that carry out specific functions. We recently identified the first widely expressed H2B histone variant, H2BE and found that it promotes transcription and is critical for neuronal function and long-term memory. However, how H2BE is regulated by extracellular stimuli and whether it controls activity-dependent transcription and cellular plasticity remain unknown. We used CUT&Tag and RNA-sequencing of primary neurons, single-nucleus sequencing of cortical tissue, and multielectrode array recordings to interrogate the expression of H2BE in response to stimuli and the role of H2BE in activity-dependent gene expression and plasticity. We find that unlike Further, we show that neurons lacking H2BE are unable to mount proper long-term activity-dependent transcriptional responses both in cultured neurons and in animal models. Lastly, we demonstrate that H2BE knockout neurons fail to undergo the electrophysiological changes associated with homeostatic plasticity in neurons after long-term stimulation. In summary, these data demonstrate that H2BE expression is inversely correlated to activity and necessary for long-term activity-dependent responses, revealing the first instance of a histone variant involved in the homeostatic plasticity response in neurons.
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Project description:A cell’s ability to respond and adapt to environmental stimuli relies in part on transcriptional programs controlled by histone proteins. Histones affect transcription through numerous mechanisms including through replacement with variant forms that carry out specific functions. We recently identified the first widely expressed H2B histone variant, H2BE and found that it promotes transcription and is critical for neuronal function and long-term memory. However, how H2BE is regulated by extracellular stimuli and whether it controls activity-dependent transcription and cellular plasticity remain unknown. We used CUT&Tag and RNA-sequencing of primary neurons, single-nucleus sequencing of cortical tissue, and multielectrode array recordings to interrogate the expression of H2BE in response to stimuli and the role of H2BE in activity-dependent gene expression and plasticity. We find that unlike Further, we show that neurons lacking H2BE are unable to mount proper long-term activity-dependent transcriptional responses both in cultured neurons and in animal models. Lastly, we demonstrate that H2BE knockout neurons fail to undergo the electrophysiological changes associated with homeostatic plasticity in neurons after long-term stimulation. In summary, these data demonstrate that H2BE expression is inversely correlated to activity and necessary for long-term activity-dependent responses, revealing the first instance of a histone variant involved in the homeostatic plasticity response in neurons.
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Project description:A cell’s ability to respond and adapt to environmental stimuli relies in part on transcriptional programs controlled by histone proteins. Histones affect transcription through numerous mechanisms including through replacement with variant forms that carry out specific functions. We recently identified the first widely expressed H2B histone variant, H2BE and found that it promotes transcription and is critical for neuronal function and long-term memory. However, how H2BE is regulated by extracellular stimuli and whether it controls activity-dependent transcription and cellular plasticity remain unknown. We used CUT&Tag and RNA-sequencing of primary neurons, single-nucleus sequencing of cortical tissue, and multielectrode array recordings to interrogate the expression of H2BE in response to stimuli and the role of H2BE in activity-dependent gene expression and plasticity. We find that unlike Further, we show that neurons lacking H2BE are unable to mount proper long-term activity-dependent transcriptional responses both in cultured neurons and in animal models. Lastly, we demonstrate that H2BE knockout neurons fail to undergo the electrophysiological changes associated with homeostatic plasticity in neurons after long-term stimulation. In summary, these data demonstrate that H2BE expression is inversely correlated to activity and necessary for long-term activity-dependent responses, revealing the first instance of a histone variant involved in the homeostatic plasticity response in neurons.
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| phs001187 | dbGaP
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: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:We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment. The objective of generating this dataset was to analyze the occupancy of H2BE protein in the vicinity of gene promoters throughout the genome, relative to histone H3, in olfactory sensory neurons within the main olfactory epithelium (MOE).
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