The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring.
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Cellular and Molecular Life Sciences Open Access 11 July 2022
Nature Communications Open Access 15 June 2022
Histone macroH2A1 is a stronger regulator of hippocampal transcription and memory than macroH2A2 in mice
Communications Biology Open Access 19 May 2022
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We would like to thank M. Boroomandi for help with the behavioral experiments. We would like to thank E.E. Furlong, A.G. Ladurner, C. Margulies, R.P. Zinzen and W. Jackson for critical reading of the manuscript. This work was supported by the DFG (BO4224/4-1) (S. Bonn), the Network of Centres of Excellence in Neurodegeneration (CoEN) initiative (S. Bonn and A.F.), iMed – the Helmholtz Initiative on Personalized Medicine (S. Bonn and A.F.), the EURYI Award of the ESF (A.F.), the Hans and Ilse Breuer Foundation (A.F.), and by the European Research Council under the European Union's Seventh Framework Program (FP7/2007–2013)/ ERC Grant Agreement No. 321366-Amyloid (advanced grant to C.H.).
The authors declare no competing financial interests.
Supplementary Figures 1–30 (PDF 9692 kb)
Detailed information on the antibodies used for ChIP- and MeDIP-seq experiments and their usage. (XLS 29 kb)
Overview over all DEGs and DEEs for the different time-points, learning comparisons, and brain areas. Additional information on in vitro DEGs after KCl stimulation. (XLS 13418 kb)
Summarization of ChIP-, MeDIP-, and RNA-seq samples and their corresponding quality metrics. (XLS 88 kb)
Table containing the genes that were categorized as neuron- or glia-specific based on published information. (XLS 44 kb)
Table of the predicted cell-type specific genes in the CA1 and ACC, in neurons and non-neurons. (XLS 125 kb)
Table of the predicted cell-type specific CRMs in the CA1 and ACC, in neurons and non-neurons. (XLS 11301 kb)
Detailed information on the CRMs that cloned and validated in Danio rerio enhancer assays. (XLS 53 kb)
Lists of genes containing DHPTMs for the in vivo and in vitro data and summary information. (XLS 158 kb)
Table summarizing information of the ChIP, expression, and MeDIP qPCR primers used. (XLS 39 kb)
Information on DHPTM-DEG comparisons for the different histone modifications, learning comparisons, and cell types. (XLS 57 kb)
Overview over all DMRs for the different time-points, learning comparisons, brain areas, and cell types. (XLS 23253 kb)
Information on DMG-DEG and DMG-DEE comparisons for the different time-points, learning comparisons, brain areas, and cell types. (XLS 430 kb)
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Halder, R., Hennion, M., Vidal, R. et al. DNA methylation changes in plasticity genes accompany the formation and maintenance of memory. Nat Neurosci 19, 102–110 (2016). https://doi.org/10.1038/nn.4194
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