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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Hippocampal stimulation promotes intracellular Tip60 dynamics with concomitant genome reorganization and synaptic gene activation
Molecular and cellular neurosciences, v 101, 103412
Dec 2019
PMID: 31682915
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Genomic reorganizations mediating the engagement of target genes to transcription factories (TFs), characterized as specialized nuclear subcompartments enriched in hyperphosphorylated RNA polymerase II (RNAPII) and transcriptional regulators, act as an important layer of control in coordinating efficient gene transcription. However, their presence in hippocampal neurons and potential role in activity-dependent coregulation of genes within the brain remains unclear. Here, we investigate whether the well-characterized role for the histone acetyltransferase (HAT) Tip60 in mediating epigenetic control of inducible neuroplasticity genes involves TF associated chromatin reorganization in the hippocampus. We show that Tip60 shuttles into the nucleus following extracellular stimulation of rat hippocampal neurons with concomitant enhancement of Tip60 binding and activation of specific synaptic plasticity genes. Multicolor three-dimensional (3D) DNA fluorescent in situ hybridization (DNA-FISH) reveals that hippocampal stimulation mobilizes these same synaptic plasticity genes and Tip60 to RNAPII-rich TFs. Our data support a model by which external hippocampal stimulation promotes intracellular Tip60 HAT dynamics with concomitant TF associated genome reorganization to initiate Tip60mediated synaptic gene activation.
•Transcription factory (TF) function in activity-dependent neuroplasticity gene control in the brain is unclear.•Extracellular stimulation leads to subcellular redistribution of Tip60 within hippocampal neurons.•Tip60 is recruited to inducible neuroplasticity genes that are activated following extracellular stimulation.•Tip60 neuroplasticity gene targets associate with TFs in response to extracellular stimulation.•Neuroplasticity genes and Tip60 co-associate with the same TF following extracellular stimulation.
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Details
- Title
- Hippocampal stimulation promotes intracellular Tip60 dynamics with concomitant genome reorganization and synaptic gene activation
- Creators
- Ashley Karnay - Drexel UniversityBhanu Chandra Karisetty - Drexel UniversityMariah Beaver - Drexel UniversityFelice Elefant - Drexel University
- Publication Details
- Molecular and cellular neurosciences, v 101, 103412
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000502686400007
- Scopus ID
- 2-s2.0-85074767930
- Other Identifier
- 991019168674204721
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- Web of Science research areas
- Neurosciences