Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease
The immediate early gene Arc is a master regulator of synaptic function and a critical determinant of memory consolidation. Here, we show that Arc interacts with dynamic chromatin and closely associates with histone markers for active enhancers and transcription in cultured rat hippocampal neurons....
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/8/1946 |
| _version_ | 1797432433852809216 |
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| author | How-Wing Leung Gabriel Foo Antonius VanDongen |
| author_facet | How-Wing Leung Gabriel Foo Antonius VanDongen |
| author_sort | How-Wing Leung |
| collection | DOAJ |
| description | The immediate early gene Arc is a master regulator of synaptic function and a critical determinant of memory consolidation. Here, we show that Arc interacts with dynamic chromatin and closely associates with histone markers for active enhancers and transcription in cultured rat hippocampal neurons. Both these histone modifications, H3K27Ac and H3K9Ac, have recently been shown to be upregulated in late-onset Alzheimer’s disease (AD). When Arc induction by pharmacological network activation was prevented using a short hairpin RNA, the expression profile was altered for over 1900 genes, which included genes associated with synaptic function, neuronal plasticity, intrinsic excitability, and signalling pathways. Interestingly, about 100 Arc-dependent genes are associated with the pathophysiology of AD. When endogenous Arc expression was induced in HEK293T cells, the transcription of many neuronal genes was increased, suggesting that Arc can control expression in the absence of activated signalling pathways. Taken together, these data establish Arc as a master regulator of neuronal activity-dependent gene expression and suggest that it plays a significant role in the pathophysiology of AD. |
| first_indexed | 2024-03-09T10:00:29Z |
| format | Article |
| id | doaj.art-7311dd82ee0845ef946f8a9de967bfc4 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:00:29Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-7311dd82ee0845ef946f8a9de967bfc42023-12-01T23:28:06ZengMDPI AGBiomedicines2227-90592022-08-01108194610.3390/biomedicines10081946Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s DiseaseHow-Wing Leung0Gabriel Foo1Antonius VanDongen2Duke-NUS Medical School, Singapore 169857, SingaporeDuke-NUS Medical School, Singapore 169857, SingaporeDuke-NUS Medical School, Singapore 169857, SingaporeThe immediate early gene Arc is a master regulator of synaptic function and a critical determinant of memory consolidation. Here, we show that Arc interacts with dynamic chromatin and closely associates with histone markers for active enhancers and transcription in cultured rat hippocampal neurons. Both these histone modifications, H3K27Ac and H3K9Ac, have recently been shown to be upregulated in late-onset Alzheimer’s disease (AD). When Arc induction by pharmacological network activation was prevented using a short hairpin RNA, the expression profile was altered for over 1900 genes, which included genes associated with synaptic function, neuronal plasticity, intrinsic excitability, and signalling pathways. Interestingly, about 100 Arc-dependent genes are associated with the pathophysiology of AD. When endogenous Arc expression was induced in HEK293T cells, the transcription of many neuronal genes was increased, suggesting that Arc can control expression in the absence of activated signalling pathways. Taken together, these data establish Arc as a master regulator of neuronal activity-dependent gene expression and suggest that it plays a significant role in the pathophysiology of AD.https://www.mdpi.com/2227-9059/10/8/1946Alzheimer’s diseasememorychromatintranscription |
| spellingShingle | How-Wing Leung Gabriel Foo Antonius VanDongen Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease Biomedicines Alzheimer’s disease memory chromatin transcription |
| title | Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease |
| title_full | Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease |
| title_fullStr | Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease |
| title_full_unstemmed | Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease |
| title_short | Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer’s Disease |
| title_sort | arc regulates transcription of genes for plasticity excitability and alzheimer s disease |
| topic | Alzheimer’s disease memory chromatin transcription |
| url | https://www.mdpi.com/2227-9059/10/8/1946 |
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