Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chromatin plasticity contributes to neuronal selection during memory allocation

ABSTRACT: Memory allocation refers to the process by which neurons are recruited into the encoding ensemble to store learned information. This recruitment is regulated by neuronal selection based on differences in intrinsic excitability (IE) and the expression of the transcription factor CREB. However, whether other forms of plasticity influence memory allocation remains unknown. Here, we found that chromatin compaction and histone acetylation in the mouse lateral amygdala display a high degree of heterogeneity, a prerequisite for neuronal selection. Consequently, when we increased histone acetylation by overexpressing histone acetyl transferases (HATs), neurons with elevated histone acetylation were preferentially recruited into the encoding ensemble and memory retention was enhanced, while optogenetic silencing of the epigenetically altered neurons prevented memory expression. Mechanistically, using patch-clamp recordings and single-nucleus multi-ome sequencing, we observed that HAT overexpression increased IE and epitranscriptomic changes favoring synaptic plasticity. Lastly, by merging FRET-based epigenetic beacons with calcium indicators to simultaneously record histone acetylation and neuronal dynamics in real time, we found that epigenetic heterogeneity underlies IE in cell-autonomous manner. These results identify chromatin plasticity as a key factor catalyzing memory allocation.

ORGANISM(S): Mus musculus

PROVIDER: GSE220696 | GEO | 2024/07/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and long-term memory [ChIP-seq]

Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and directchum regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Genome-wide examination of histone H3 and H4 acetylation, as well as ACSS2 binding, in undifferentiated CAD cells and differentiated CAD neurons; background adjusted by H3 ChIP or Input.

2017-05-01 | E-GEOD-76850 | biostudies-arrayexpress

Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and long-term memory [RNA-seq]

Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Global survey of gene expression in CAD cells and differentiated CAD neurons following lentiviral knockdown of ACSS2 or ATP citrate lyase (ACL) (and control = scramble hairpin); survey of hippocampal gene expression changes associated with retrieval of fear memory, after ACSS2-AAV knockdown or in EGFP-AAV control (comparison of 0h vs. 1h post-memory retrieval).

2017-05-01 | E-GEOD-76853 | biostudies-arrayexpress

Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and long-term memory [RNA-seq]

Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation.

2017-05-01 | GSE76853 | GEO

Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and long-term memory [ChIP-seq]

2017-05-01 | GSE76850 | GEO

Acetyl CoA metabolism by ACSS2 regulates neuronal histone acetylation and hippocampal memory [RNA-seq In Vivo]

Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of mammalian spatial object memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory, and these hippocampal genes are pre-bound by ACSS2. These results reveal a unique connection between cellular metabolism, gene regulation, and neural plasticity, establishing a link between generation of acetyl-CoA “on-site” at chromatin of critical neuronal genes.

2017-05-01 | GSE90855 | GEO

Acetyl CoA metabolism by ACSS2 regulates neuronal histone acetylation and hippocampal memory [RNA-seq In Vitro]

Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of mammalian spatial object memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory, and these hippocampal genes are pre-bound by ACSS2. These results reveal a unique connection between cellular metabolism, gene regulation, and neural plasticity, establishing a link between generation of acetyl-CoA “on-site” at chromatin of critical neuronal genes.

2017-05-01 | GSE90854 | GEO

Acetyl CoA metabolism by ACSS2 regulates neuronal histone acetylation and hippocampal memory [in vivo ChIP-seq]

Project description:Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of mammalian spatial object memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory, and these hippocampal genes are pre-bound by ACSS2. These results reveal a unique connection between cellular metabolism, gene regulation, and neural plasticity, establishing a link between generation of acetyl-CoA “on-site” at chromatin of critical neuronal genes.

2017-05-01 | GSE90853 | GEO

Chromatin plasticity contributes to neuronal selection during memory allocation

Project description:Chromatin plasticity contributes to neuronal selection during memory allocation

| PRJNA911184 | ENA

Epigenetic correction of defective plasticity in a tauopathy mouse model with an acetyltransferase activator [RNA-Seq]

Project description:In the adult brain, histone acetylation is associated with activity-regulated transcriptional changes that are required for synaptic plasticity and memory. These processes are dismantled in neurodegenerative diseases. Here, we demonstrate that synaptic plasticity and memory deficiencies can be restored in a mouse model of tauopathy following treatment with CSP-TTK21, a small molecule activator of CBP/p300 histone acetyltransferases (HAT). CSP-TTK21 normalized the H2B acetylation levels in many genes, including a series of super-enhancer –regulated genes, associated with plasticity and neuronal function in resting tauopathic mice. CSP-TTK21 re-established part of the learning-induced hippocampal transcriptome, including the induction of immediate early genes and memory-related genes, and the down-regulation of neuronal identity genes that bear super-enhancers. This study is the first to provide in vivo proof-of-concept evidence that direct activation of CBP/p300 HAT efficiently and selectively reverses epigenetic, transcriptional, synaptic plasticity, and behavioral deficits associated to Alzheimer’s disease lesions in mice.

2018-11-05 | GSE103359 | GEO

Epigenetic correction of defective plasticity in a tauopathy mouse model with an acetyltransferase activator [ChIP-Seq]

2018-11-05 | GSE103358 | GEO