Histone Hypervariants H2A.Z.1 and H2A.Z.2 Play Independent and Context-Specific Roles in Neuronal Activity-Induced Transcription of Arc/ Arg3.1 and Other Immediate Early Genes

Simple item page
dc.contributor.authorDunn, Carissa J.en
dc.contributor.authorSarkar, Pushpitaen
dc.contributor.authorBailey, Emma R.en
dc.contributor.authorFarris, Shannonen
dc.contributor.authorZhao, Meilanen
dc.contributor.authorWard, James M.en
dc.contributor.authorDudek, Serena M.en
dc.contributor.authorSaha, Ramendra N.en
dc.date.accessioned2019-06-03T21:02:50Zen
dc.date.available2019-06-03T21:02:50Zen
dc.date.issued2017en
dc.description.abstractThe histone variant H2A.Z is an essential and conserved regulator of eukaryotic gene transcription. However, the exact role of this histone in the transcriptional process remains perplexing. In vertebrates, H2A.Z has two hypervariants, H2A.Z.1 and H2A.Z.2, that have almost identical sequences except for three amino acid residues. Due to such similarity, functional specificity of these hypervariants in neurobiological processes, if any, remain largely unknown. In this study with dissociated rat cortical neurons, we asked if H2A.Z hypervariants have distinct functions in regulating basal and activity-induced gene transcription. Hypervariant-specific RNAi and microarray analyses revealed that H2A.Z.1 and H2A.Z.2 regulate basal expression of largely nonoverlapping gene sets, including genes that code for several synaptic proteins. In response to neuronal activity, rapid transcription of our model gene Arc is impaired by depletion of H2A.Z.2, but not H2A.Z.1. This impairment is partially rescued by codepletion of the H2A.Z chaperone, ANP32E. In contrast, under a different context (after 48 h of tetrodotoxin, TTX), rapid transcription of Arc is impaired by depletion of either hypervariant. Such context-dependent roles of H2A.Z hypervariants, as revealed by our multiplexed gene expression assays, are also evident with several other immediate early genes, where regulatory roles of these hypervariants vary from gene to gene under different conditions. Together, our data suggest that H2A.Z hypervariants have context-specific roles that complement each other to mediate activity-induced neuronal gene transcription.en
dc.format.extent30 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1523/ENEURO.0040-17.2017en
dc.identifier.issue4en
dc.identifier.urihttp://hdl.handle.net/10919/89697en
dc.identifier.volume4en
dc.language.isoenen
dc.publisherSociety for Neuroscienceen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectArcen
dc.subjectepigeneticsen
dc.subjectH2A.Zen
dc.subjectH2A.Z.1en
dc.subjectH2A.Z.2en
dc.subjecthistoneen
dc.titleHistone Hypervariants H2A.Z.1 and H2A.Z.2 Play Independent and Context-Specific Roles in Neuronal Activity-Induced Transcription of Arc/ Arg3.1 and Other Immediate Early Genesen
dc.title.serialeNeuroen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
ENEURO.0040-17.2017.pdf
Size:
5.88 MB
Format:
Adobe Portable Document Format
Download

Collections

Scholarly Works, Fralin Biomedical Research Institute at VTC