Cloning and Characterization of the Histone Acetyltransferase Human Homolog Dmel\TIP60 in Drosophila melanogaster: Dmel\TIP60 Is Essential for Multicellular Development

• Published in: Genetics (Austin) 2007-03, Vol.175 (3), p.1229-1240
• Main Authors: Zhu, X, Singh, N, Donnelly, C, Boimel, P, Elefant, F
• Format: Article
• Language: English
• Subjects: acyltransferases; Alzheimer's disease; Amino Acid Sequence; Animals; Apoptosis; Base Sequence; Cell Line; Chromatin; Chromatin Assembly and Disassembly - genetics; Cloning, Molecular; Crosses, Genetic; DNA Primers; DNA repair; DNA, Complementary - genetics; Drosophila melanogaster; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; embryogenesis; Embryonic Development - genetics; Gene expression; Gene Expression Regulation, Developmental - genetics; genes; Genes, Essential - genetics; Genetics; histone acetyltransferase; Histone Acetyltransferases - genetics; insect development; Investigations; messenger RNA; molecular cloning; Molecular Sequence Data; nucleotide sequences; Prostate cancer; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Roles; Sequence Alignment; Sequence Analysis, DNA
• ISSN: 0016-6731; 1943-2631; 1943-2631
• DOI: 10.1534/genetics.106.063685

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 for effectively studying the roles of TIP60 in specific tissues and cell types during development.