Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation

Wee, Caroline Lei; Teo, Shaun Y M; Oey, Nicodemus Edrick; Wright, Graham D.; VanDongen, Hendrika M.A.; VanDongen, Antonius M.J.

doi:10.1523/eneuro.0019-14.2014

Cited by 46 publications

(46 citation statements)

References 66 publications

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“…We find that strong training employs KAT5 acetyltransferase and H4K12 acetylation, which is confirmed by the report that KAT5 mediates H4K5 and H4K12 acetylation (Grezy et al, 2016; Kouzarides, 2007; Wee et al, 2014). Thus, weak training induces H3K14 acetylation by CBP at the Fgf1b and c-fos promoters, whereas strong training induces H4K12 acetylation by KAT5 at the Fgf1b promoter.…”

Section: Discussionsupporting

confidence: 90%

“…Deficits in microtubule-mediated intracellular transport impair synaptic plasticity and memory formation (Shumyatsky et al, 2005; Uchida et al, 2014; Uchida and Shumyatsky, 2015), suggesting that nuclear translocation of CRTC1 may be dependent on microtubules. Injection of nocodazole, a microtubule destabilizer, into the hippocampus 1 h before 3-shock CFC blocked the increase in nuclear CRTC1 and the decrease in synaptic CRTC1 but did not change whole-cell CRTC1 levels, as measured 1 h following CFC (Figure S5H).…”

Section: Resultsmentioning

confidence: 99%

“…Given that ChIP assay indicated enrichment of acetylated H4K5 and H4K12 at the Fgf1b promoter by strong but not weak CFC, we examined histone acetyltransferase KAT5, which is known to enhance H4K5 and H4K12 acetylation (Grezy et al, 2016; Kouzarides, 2007; Wee et al, 2014). ChIP assay revealed KAT5 recruitment to the Fgf1b promoter 2 h following 3-shock CFC but not 1-shock CFC (Figure 5I), while there was no difference in recruitment to the c-fos promoter (Figure 5J).…”

Section: Resultsmentioning

confidence: 99%

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CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

et al. 2017

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SUMMARY Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription factor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3–N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

et al. 2017

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“…4Ai, 4Bi, 4Aii, and 4Bii). Tip60 preferential acetylated lysine residues (Anamika et al 2010) H4K16 (Renaud et al 2016) and H4K12 (Wee et al 2014) levels were also significantly reduced throughout Aβ42 neurodegeneration progression, and these alterations were protected against ( Fig. 4Aiii, 4Biii, and Supplemental Fig.…”

Section: Tip60/hdac2 Balance Is Disrupted During Early Aβ42-induced Nmentioning

confidence: 94%

Tip60 protects against amyloid-β peptide-induced transcriptomic alterations via different modes of action in early versus late stages of neurodegenerative progression

Zhang

Karisetty

Bhatnagar

et al. 2020

Preprint

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Alzheimer's disease is an age-related neurodegenerative disorder hallmarked by amyloid-β (Aβ) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between the histone acetyltransferases (HAT) Tip60 and histone deacetylase 2 (HDAC2), can directly contribute to AD pathology. Nevertheless, early and late-stage regulatory epigenetic alterations remain to be characterized. Here we profile Tip60 HAT/HDAC2 dynamics and transcriptional changes across early and late stage AD pathology in the Drosophila brain produced solely by human amyloid-β42.We show that early Aβ42 induction leads to disruption of Tip60 HAT/HDAC2 balance during early neurodegenerative stages preceding Aβ plaque accumulation that persists into late AD stages.Correlative transcriptome studies reveal alterations in biological processes we classified as transient (early-stage only), late-onset (late-stage only), and constant (both). Increasing Tip60 HAT levels in the Aβ42 fly brain protects against AD functional pathologies that include Aβ plaque accumulation, neural cell death, cognitive deficits, and shorter life-span. Strikingly, Tip60 also protects against Aβ42 induced transcriptomic alterations via distinct mechanisms during early and late stages of neurodegeneration. Our findings provide new insights into distinct modes of epigenetic gene alterations and Tip60 neuroprotection during early versus late stages in AD progression.

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“…In order to further understand the role of H4K12ac, blocking of alcohol-induced H4K12ac was needed. For this purpose, according to literature, amongst other histone acetyltransferases, TIP60 was found to be most responsible for acetylation of H4K12 (Altaf et al, 2010, Wee et al, 2014.…”

Section: Chronic Treatment With Histone Acetyltransferase Inhibitor Nmentioning

confidence: 93%

Epigenetic Mechanisms Regulating the Functional Effects of Chronic Alcohol Exposure of Human Monocyte-derived Dendritic Cells

Parira¹

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Nuclear Arc Interacts with the Histone Acetyltransferase Tip60 to Modify H4K12 Acetylation

Cited by 46 publications

References 66 publications

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

Tip60 protects against amyloid-β peptide-induced transcriptomic alterations via different modes of action in early versus late stages of neurodegenerative progression

Epigenetic Mechanisms Regulating the Functional Effects of Chronic Alcohol Exposure of Human Monocyte-derived Dendritic Cells

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