Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury
Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT) and deacetylase activities (HDAC). Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation s...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2014
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| Online Access: | http://hdl.handle.net/1721.1/88169 |
| _version_ | 1811096318782734336 |
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| author | Yildirim, Ferah Ji, Shengbo Kronenberg, Golo Barco, Angel Olivares, Roman Benito, Eva Dirnagl, Ulrich Gertz, Karen Endres, Matthias Harms, Christoph Meisel, Andreas |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Yildirim, Ferah Ji, Shengbo Kronenberg, Golo Barco, Angel Olivares, Roman Benito, Eva Dirnagl, Ulrich Gertz, Karen Endres, Matthias Harms, Christoph Meisel, Andreas |
| author_sort | Yildirim, Ferah |
| collection | MIT |
| description | Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT) and deacetylase activities (HDAC). Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation status of histones. In the present study, we characterized the changes in histone acetylation levels in ischemia models of focal cerebral ischemia and identified cAMP-response element binding protein (CREB)–binding protein (CBP) as a crucial factor in the susceptibility of neurons to ischemic stress. Both neuron-specific RNA interference and neurons derived from CBP heterozygous knockout mice showed increased damage after oxygen-glucose deprivation (OGD) in vitro. Furthermore, we demonstrated that ischemic preconditioning by a short (5 min) subthreshold occlusion of the middle cerebral artery (MCA), followed 24 h afterwards by a 30 min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic preconditioning enhanced CBP recruitment and histone acetylation at the promoter of the neuroprotective gene gelsolin leading to increased gelsolin expression in neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic preconditioning. Taken together, our findings suggest that the levels of CBP and histone acetylation determine stroke outcome and are crucially associated with the induction of an ischemia-resistant state in neurons. |
| first_indexed | 2024-09-23T16:41:56Z |
| format | Article |
| id | mit-1721.1/88169 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:41:56Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/881692022-10-03T07:40:05Z Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury Yildirim, Ferah Ji, Shengbo Kronenberg, Golo Barco, Angel Olivares, Roman Benito, Eva Dirnagl, Ulrich Gertz, Karen Endres, Matthias Harms, Christoph Meisel, Andreas Massachusetts Institute of Technology. Department of Biological Engineering Yildirim, Ferah Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT) and deacetylase activities (HDAC). Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation status of histones. In the present study, we characterized the changes in histone acetylation levels in ischemia models of focal cerebral ischemia and identified cAMP-response element binding protein (CREB)–binding protein (CBP) as a crucial factor in the susceptibility of neurons to ischemic stress. Both neuron-specific RNA interference and neurons derived from CBP heterozygous knockout mice showed increased damage after oxygen-glucose deprivation (OGD) in vitro. Furthermore, we demonstrated that ischemic preconditioning by a short (5 min) subthreshold occlusion of the middle cerebral artery (MCA), followed 24 h afterwards by a 30 min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic preconditioning enhanced CBP recruitment and histone acetylation at the promoter of the neuroprotective gene gelsolin leading to increased gelsolin expression in neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic preconditioning. Taken together, our findings suggest that the levels of CBP and histone acetylation determine stroke outcome and are crucially associated with the induction of an ischemia-resistant state in neurons. German Research Foundation (Exc 257) Germany. Federal Ministry of Education and Research (01 EO 08 01) Hermann von Helmholtz-Gemeinschaft Deutscher Forschungszentren (SO-022NG) European Union (7th Framework Programme (FP7/2007–2013) grant agreement no. 201024) 2014-07-01T18:38:53Z 2014-07-01T18:38:53Z 2014-04 2013-11 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/88169 Yildirim, Ferah, Shengbo Ji, Golo Kronenberg, Angel Barco, Roman Olivares, Eva Benito, Ulrich Dirnagl, et al. “Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance Against Ischemic Injury.” Edited by Christoph Kleinschnitz. PLoS ONE 9, no. 4 (April 18, 2014): e95465. en_US http://dx.doi.org/10.1371/journal.pone.0095465 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Yildirim, Ferah Ji, Shengbo Kronenberg, Golo Barco, Angel Olivares, Roman Benito, Eva Dirnagl, Ulrich Gertz, Karen Endres, Matthias Harms, Christoph Meisel, Andreas Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury |
| title | Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury |
| title_full | Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury |
| title_fullStr | Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury |
| title_full_unstemmed | Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury |
| title_short | Histone Acetylation and CREB Binding Protein Are Required for Neuronal Resistance against Ischemic Injury |
| title_sort | histone acetylation and creb binding protein are required for neuronal resistance against ischemic injury |
| url | http://hdl.handle.net/1721.1/88169 |
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