Genetics. Published Articles Ahead of Print: December 18, 2006, Copyright © 2006
doi:10.1534/genetics.106.063685


A more recent version of this article appeared on March 1, 2007.

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The Cloning and Characterization of the Histone Acetyltransferase Human Homolog Dmel/TIP60 in Drosophila melanogaster: Dmel/TIP60 is Essential for Multicellular Development

Xianmin Zhu 1, Neetu Singh 1, Christopher Donnely 1, Pamela Boimel 1 and Felice Elefant 1*

1 Drexel University

* To whom correspondence should be addressed. E-mail: fe22{at}drexel.edu.

Submitted on July 18, 2006
Revised on October 3, 2006
Accepted on 14 December 2006


Abstract

Chromatin packaging directly influences gene programming as it permits only certain portions of the genome to be activated in any given developmental stage, cell, and tissue-type. Histone acetyltransferases (HATs) are a key class of chromatin regulatory proteins that mediate such developmental chromatin control, however their specific roles during multicellular development remain unclear. Here, we report the first isolation and developmental characterization of a Drosophila HAT gene (Dmel/TIP60) that is the homolog of the human HAT gene TIP60. We show that Dmel/TIP60 is differentially expressed during Drosophila development, with transcript levels significantly peaking during embryogenesis. We further demonstrate that reducing endogenous Dmel/TIP60 expression in Drosophila embryonic cells by RNAi results in cellular defects and lethality. Finally, using a GAL4 targeted RNAi system in Drosophila, we show that ubiquitous or mesoderm/muscle specific reduction of Dmel/TIP60 expression results in lethality during fly development. Our results suggest a mechanism for HAT regulation involving developmental control of HAT expression profiles, and show that Dmel/TIP60 is essential for multicellular development. Significantly, our inducible and targeted HAT knockdown system in Drosophila now provides a powerful tool to effectively study the roles of these chromatin mediators in specific tissues and cell types during development.

Key Words: Development, Dmel/Tip60, Drosophila, Histone Acetyltransferases