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Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism

BACKGROUND: 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 rema...

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Autores principales: Lorbeck, Meridith, Pirooznia, Keerthy, Sarthi, Jessica, Zhu, Xianmin, Elefant, Felice
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073973/
https://www.ncbi.nlm.nih.gov/pubmed/21494552
http://dx.doi.org/10.1371/journal.pone.0018412
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author Lorbeck, Meridith
Pirooznia, Keerthy
Sarthi, Jessica
Zhu, Xianmin
Elefant, Felice
author_facet Lorbeck, Meridith
Pirooznia, Keerthy
Sarthi, Jessica
Zhu, Xianmin
Elefant, Felice
author_sort Lorbeck, Meridith
collection PubMed
description BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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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spelling pubmed-30739732011-04-14 Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism Lorbeck, Meridith Pirooznia, Keerthy Sarthi, Jessica Zhu, Xianmin Elefant, Felice PLoS One Research Article BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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. Public Library of Science 2011-04-11 /pmc/articles/PMC3073973/ /pubmed/21494552 http://dx.doi.org/10.1371/journal.pone.0018412 Text en Lorbeck et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lorbeck, Meridith
Pirooznia, Keerthy
Sarthi, Jessica
Zhu, Xianmin
Elefant, Felice
Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism
title Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism
title_full Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism
title_fullStr Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism
title_full_unstemmed Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism
title_short Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism
title_sort microarray analysis uncovers a role for tip60 in nervous system function and general metabolism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073973/
https://www.ncbi.nlm.nih.gov/pubmed/21494552
http://dx.doi.org/10.1371/journal.pone.0018412
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