2018
DOI: 10.1016/j.celrep.2018.01.020
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Learning and Age-Related Changes in Genome-wide H2A.Z Binding in the Mouse Hippocampus

Abstract: Summary Histone variants were recently discovered to regulate neural plasticity, with H2A.Z emerging as a memory suppressor. Using whole-genome sequencing of the mouse hippocampus, we show that basal H2A.Z occupancy is positively associated with steady-state transcription, whereas learning-induced H2A.Z removal is associated with learning-induced gene expression. AAV-mediated H2A.Z depletion enhanced fear memory and resulted in gene-specific alterations of learning-induced transcription, reinforcing the role o… Show more

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Cited by 78 publications
(120 citation statements)
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“…Since these genes are actively expressed in hippocampal tissue, it follows that there is almost no DNA methylation around their TSSs (Figure 4b). Nucleosomes surrounding active TSSs often contain the H2A.Z histone variant, and of the 893 DMR identified due to Tet2 knockout, 481 overlap with H2A.Z binding sites identified in the hippocampus (Stefanelli et al, 2018). WGBS allows for the interrogation of DNA methylation with single cytosine resolution, and we found that changes in methylation across these DMRs can occur broadly or at a subset of CpG sites within the 25 CpG window (Figure 4c).…”
Section: The Conditional Knockout Of Tet2 In Glutamatergic Neurons Enmentioning
confidence: 74%
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“…Since these genes are actively expressed in hippocampal tissue, it follows that there is almost no DNA methylation around their TSSs (Figure 4b). Nucleosomes surrounding active TSSs often contain the H2A.Z histone variant, and of the 893 DMR identified due to Tet2 knockout, 481 overlap with H2A.Z binding sites identified in the hippocampus (Stefanelli et al, 2018). WGBS allows for the interrogation of DNA methylation with single cytosine resolution, and we found that changes in methylation across these DMRs can occur broadly or at a subset of CpG sites within the 25 CpG window (Figure 4c).…”
Section: The Conditional Knockout Of Tet2 In Glutamatergic Neurons Enmentioning
confidence: 74%
“…An analysis of the percent methylation of DMRs that reside +/-2kb around transcriptional start sites (TSSs) indicated increased methylation across promoters and especially around TSSs (Figure 3f). DMRs were even more associated with the histone variant H2A.Z (Figure 3g), which is found in the +1 and -1 nucleosomes at transcriptional start sites in the hippocampus and is ejected at ERGs after experiential learning (Stefanelli et al, 2018). Unsurprisingly, given the tight association of H2A.Z and unmethylated CpG islands (oe >0.6), DMRs were also concentrated at CpG islands (Figure 3h), with 77% of the DMRs being hypermethylated.…”
Section: The Conditional Knockout Of Tet2 In Glutamatergic Neurons Enmentioning
confidence: 97%
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“…Although alterations in chromatin landscape with aging have been reported, few studies have mapped altered histone marks with age. H2A.Z, a histone variant needed for the acetylation of histone 3 lysine 27 [94], do change with aging in the hippocampus [95], and may be a contributing mechanism to enhancer mark changes with aging. Given these results we hypothesize that changes in methylation can potentially alter transcription through attenuation of enhancer strength rather than facilitating deposition of H3K27ac.…”
Section: Enhancer Age-dmrs Are Related To Age-degsmentioning
confidence: 99%
“…Only WT control and experimental groups were used. ChIP-sequencing data of hippocampal histone marks was obtained from GEO:GSE85873 (H3K4me3 and H3K27me3) [118], GEO:GSE103358 (H2Bac), and GEO:GSE100039 (H2A.Z) [95]. Cortex epigenetic marks including H3K27ac, H3K36me3, and H3K9me3 were obtained from GEO: GSE103214 [119].…”
Section: Public Data Acquisitionmentioning
confidence: 99%