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Journal Article

TIP60/KAT5 is required for neuronal viability in hippocampal CA1.

MPS-Authors
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Urban,  I.
Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society;

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Thaller,  C.
Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society;

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Eichele,  G.
Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society;

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3175912.pdf
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Supplementary Material (public)

3175912_Suppl.htm
(Supplementary material), 376KB

Citation

Urban, I., Kerimoglu, C., Sakib, M. S., Wang, H., Benito, E., Thaller, C., et al. (2019). TIP60/KAT5 is required for neuronal viability in hippocampal CA1. Scientific Reports, 9: 16173. doi:10.1038/s41598-019-50927-1.


Cite as: http://hdl.handle.net/21.11116/0000-0005-179C-2
Abstract
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.