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Microarray analysis uncovers a role for Tip60 in nervous system function and general metabolism
Journal article   Open access

Microarray analysis uncovers a role for Tip60 in nervous system function and general metabolism

Meridith Lorbeck, Keerthy Pirooznia, Jessica Sarthi, Xianmin Zhu and Felice Elefant
PloS one, v 6(4), pp e18412-e18412
11 Apr 2011
PMID: 21494552
url
https://doi.org/10.1371/journal.pone.0018412View
Published, Version of Record (VoR) Open

Abstract

Multigene Family - genetics Reproducibility of Results Genes, Insect - genetics Oligonucleotide Array Sequence Analysis Animals, Genetically Modified Humans Nervous System - metabolism Drosophila melanogaster - cytology Gene Expression Regulation Histone Acetyltransferases - genetics Gene Expression Profiling Drosophila Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction Protein Transport Drosophila melanogaster - metabolism Mutant Proteins Animals Histone Acetyltransferases - metabolism Drosophila melanogaster - growth & development Transcription, Genetic Acetylation Drosophila Proteins - genetics Histones - metabolism Genes, Dominant - genetics
Tip60 is a key histone acetyltransferase (HAT) enzyme that plays a central role in diverse biological processes critical for general cell function; however, the chromatin-mediated cell-type specific developmental pathways that are dependent exclusively upon the HAT activity of Tip60 remain to be explored. Here, we investigate the role of Tip60 HAT activity in transcriptional control during multicellular development in vivo by examining genome-wide changes in gene expression in a Drosophila model system specifically depleted for endogenous dTip60 HAT function. We show that amino acid residue E431 in the catalytic HAT domain of dTip60 is critical for the acetylation of endogenous histone H4 in our fly model in vivo, and demonstrate that dTip60 HAT activity is essential for multicellular development. Moreover, our results uncover a novel role for Tip60 HAT activity in controlling neuronal specific gene expression profiles essential for nervous system function as well as a central regulatory role for Tip60 HAT function in general metabolism.

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Web of Science research areas
Biochemistry & Molecular Biology
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