TIP60/KAT5 is required for neuronal viability in hippocampal CA1
Aberrant histone acetylation contributes to age-dependent cognitive decline and neurodegenerative diseases. We analyze the function of lysine acetyltransferase TIP60/KAT5 in neurons of the hippocampus using an inducible mouse model. TIP60-deficiency in the adult forebrain leads within days to extens...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
07 November 2019
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| In: |
Scientific reports
Year: 2019, Volume: 9 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-50927-1 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41598-019-50927-1 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41598-019-50927-1 
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| Author Notes: | Inga Urban, Cemil Kerimoglu, M. Sadman Sakib, Haifang Wang, Eva Benito, Christina Thaller, Xunlei Zhou, Jun Yan, André Fischer & Gregor Eichele |
| Summary: | Aberrant histone acetylation contributes to age-dependent cognitive decline and neurodegenerative diseases. We analyze the function of lysine acetyltransferase TIP60/KAT5 in neurons of the hippocampus using an inducible mouse model. TIP60-deficiency in the adult forebrain leads within days to extensive transcriptional dysfunction characterized by the presence of a neurodegeneration-related signature in CA1. Cell cycle- and immunity-related genes are upregulated while learning- and neuronal plasticity-related genes are downregulated. The dysregulated genes seen under TIP60-deficiency overlap with those in the well-characterized CK-p25 neurodegeneration model. We found that H4K12 is hypoacetylated at the transcriptional start sites of those genes whose expression is dampened in TIP60-deficient mice. Transcriptional dysregulation is followed over a period of weeks by activation of Caspase 3 and fragmentation of β-actin in CA1 neurites, eventually leading to severe neuronal loss. TIP60-deficient mice also develop mild memory impairment. These phenotypes point to a central role of TIP60 in transcriptional networks that are critical for neuronal viability. |
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| Item Description: | Gesehen am 27.04.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-50927-1 |