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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.
Dunn, Carissa J; Sarkar, Pushpita; Bailey, Emma R; Farris, Shannon; Zhao, Meilan; Ward, James M; Dudek, Serena M; Saha, Ramendra N.
Afiliación
  • Dunn CJ; Molecular and Cell Biology Unit, School of Natural Sciences, University of California at Merced, Merced, CA 95343.
  • Sarkar P; Molecular and Cell Biology Unit, School of Natural Sciences, University of California at Merced, Merced, CA 95343.
  • Bailey ER; Laboratory of Neurobiology, NIEHS, NIH, Research Triangle Park, NC 27709.
  • Farris S; Laboratory of Neurobiology, NIEHS, NIH, Research Triangle Park, NC 27709.
  • Zhao M; Laboratory of Neurobiology, NIEHS, NIH, Research Triangle Park, NC 27709.
  • Ward JM; Integrative Bioinformatics Support Group, NIEHS, NIH, Research Triangle Park, NC 27709.
  • Dudek SM; Laboratory of Neurobiology, NIEHS, NIH, Research Triangle Park, NC 27709.
  • Saha RN; Molecular and Cell Biology Unit, School of Natural Sciences, University of California at Merced, Merced, CA 95343.
eNeuro ; 4(4)2017.
Article en En | MEDLINE | ID: mdl-28856239
The 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Histonas / Transmisión Sináptica / Proteínas del Citoesqueleto / Proteínas del Tejido Nervioso / Neuronas Límite: Animals Idioma: En Revista: ENeuro Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Histonas / Transmisión Sináptica / Proteínas del Citoesqueleto / Proteínas del Tejido Nervioso / Neuronas Límite: Animals Idioma: En Revista: ENeuro Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos