Chromatin profiling in human neurons reveals aberrant roles for histone acetylation and BRD4 in schizophrenia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA604258 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10997453.fastq.gz | Fastqsanger.gz | |||
| SRR10997454.fastq.gz | Fastqsanger.gz | |||
| SRR10997455.fastq.gz | Fastqsanger.gz | |||
| SRR10997456.fastq.gz | Fastqsanger.gz | |||
| SRR10997457.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Schizophrenia (SZ) is a psychiatric disorder with complex genetic risk dictated by interactions between hundreds of risk variants. Epigenetic factors, such as histone posttranslational modifications (PTMs), have been shown to play critical roles in many neurodevelopmental processes, and when perturbed may also contribute to the precipitation of disease. Here, we applied an unbiased proteomics approach to evaluate combinatorial histone PTMs in human induced pluripotent stem cell (hiPSC)-derived forebrain neurons from individuals with SZ. We observed hyper-acetylation of H2A.Z and H4 in neurons derived from SZ cases, results that were confirmed in postmortem human brain. We demonstrated that the bromodomain containing protein, BRD4, is a bona fide ‘reader’ of H2A.Z acetylation, and further provide evidence that BRD4 inhibition ameliorates transcriptional abnormalities in patient-derived neurons and improves sensorimotor gating behavior in mice. Thus, treatments aimed at alleviating BRD4 interactions with hyperacetylated histones may aid in the prevention or treatment of SZ.
2022-01-12 | GSE144639 | GEO
Project description:Schizophrenia (SZ) is a psychiatric disorder with complex genetic risk dictated by interactions between hundreds of risk variants. Epigenetic factors, such as histone posttranslational modifications (PTMs), have been shown to play critical roles in many neurodevelopmental processes, and when perturbed may also contribute to the precipitation of disease. Here, we apply an unbiased proteomics approach to evaluate combinatorial histone PTMs in human induced pluripotent stem cell (hiPSC)-derived forebrain neurons from individuals with SZ. We observe hyper-acetylation of H2A.Z and H4 in neurons derived from SZ cases, results that were confirmed in postmortem human brain. We demonstrate that the bromodomain and extraterminal (BET) protein, BRD4, is a bona fide ‘reader’ of H2A.Z acetylation, and further provide evidence that BET family protein inhibition ameliorates transcriptional abnormalities in patient-derived neurons. Thus, treatments aimed at alleviating BET protein interactions with hyperacetylated histones may aid in the prevention or treatment of SZ.
2022-05-06 | PXD031767 | Pride
Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
2021-06-25 | GSE164071 | GEO
Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
2021-06-25 | GSE164060 | GEO
Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
2021-06-25 | GSE164045 | GEO
Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
2021-06-25 | GSE164043 | GEO
Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
2021-06-25 | GSE164031 | GEO
Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
2021-06-25 | GSE164016 | GEO
Project description:In addition to acetylation, histones are modified by a series of competing longer chain acylations. Most of these acylation marks are enriched and co-exist with acetylation on active gene regulatory elements. Their seemingly redundant functions have hindered the understanding of histone acylations’ specific roles. Here, by using an acute lymphoblastic leukaemia (ALL) cell model and blasts from B-ALL patients, we demonstrate a role for mitochondrial activity in controlling histone acylation/acetylation ratio, especially at H4K5. An increase of the crotonylation and butyrylation over acetylation on H4K5 weakens BRD4-chromatin interaction and increases BRD4 nuclear mobility and availability for binding transcription start site associated nucleosome free regions of active genes. Our data suggest that, with regard to BRD4 dynamics, histone acylations including acetylation, should be considered collectively. A metabolism dependant control of the histone acetylation/longer chain acylation(s) ratio could constitute a common mechanism regulating bromodomain factors’ “reservoir” pool, availability and functional genomic distribution.
2021-06-25 | GSE174105 | GEO
Project description:Schizophrenia is a severe psychiatric disorder. Another study in BD has shown an aberrant pro-inflammatory status of monocytes/macrophages. Therefore, this study aimed at studying the monocyte compartment in schizophrenia, by transcription profiling of CD14+ monocytes in patients and controls.
2010-11-20 | E-MEXP-2998 | biostudies-arrayexpress