Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
PLoS One ; 6(4): e18412, 2011 Apr 11.
Article in English | MEDLINE | ID: mdl-21494552

ABSTRACT

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.


Subject(s)
Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Histone Acetyltransferases/metabolism , Nervous System/metabolism , Oligonucleotide Array Sequence Analysis , Acetylation , Animals , Animals, Genetically Modified , Drosophila Proteins/genetics , Drosophila melanogaster/cytology , Drosophila melanogaster/growth & development , Gene Expression Profiling , Gene Expression Regulation , Genes, Dominant/genetics , Genes, Insect/genetics , Histone Acetyltransferases/genetics , Histones/metabolism , Humans , Multigene Family/genetics , Mutant Proteins , Protein Transport , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic
2.
J Neurochem ; 115(2): 493-504, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20626565

ABSTRACT

The histone acetyltransferase Elp3 (Elongator Protein 3) is the catalytic subunit of the highly conserved Elongator complex. Elp3 is essential for the complex functions of Elongator in both the nucleus and cytoplasm of neurons, including the epigenetic control of neuronal motility genes and the acetylation of α-tubulin that affects axonal branching and cortical neuron migration. Accordingly, misregulation of Elp3 has been implicated in human disorders that specifically affect neuronal function, including familial dysautonomia, a disease characterized by degeneration of the sensory and autonomic nervous system, and the motor neuron degenerative disorder amyotrophic lateral sclerosis. These studies underscore the importance of Elp3 in neurodevelopment and disease, and the need to further characterize the multiple nuclear and cytoplasmic based roles of ELP3 required for neurogenesis in animal models, in vivo. In this report, we investigate the behavioral and morphological consequences that result from targeted reduction of ELP3 specifically in the developing Drosophila nervous system. We demonstrate that loss of Elp3 during neurodevelopment leads to a hyperactive phenotype and sleep loss in the adult flies, a significant expansion in synaptic bouton number and axonal length and branching in the larval neuromuscular junction as well as the misregulation of certain genes known to be involved in these processes. Our results uncover a novel role for Elp3 in the regulation of synaptic bouton expansion during neurogenesis that may be linked with a requirement for sleep.


Subject(s)
Gene Expression Regulation, Developmental/physiology , Histone Acetyltransferases/metabolism , Nerve Tissue Proteins/metabolism , Neuromuscular Junction/physiology , Presynaptic Terminals/physiology , Sleep Initiation and Maintenance Disorders/genetics , Animals , Animals, Genetically Modified , Behavior, Animal , Drosophila , Drosophila Proteins/genetics , Female , Gene Expression Regulation, Developmental/genetics , Histone Acetyltransferases/genetics , Humans , Larva , Male , Motor Activity/genetics , Nerve Tissue Proteins/genetics , Nervous System/cytology , Nervous System/enzymology , Nervous System/growth & development , Neuromuscular Junction/genetics , RNA Interference/physiology , Sleep Deprivation/genetics
3.
Gene ; 450(1-2): 8-17, 2010 Jan 15.
Article in English | MEDLINE | ID: mdl-19786080

ABSTRACT

Histone methylation plays an important role in regulating chromatin-mediated gene control and epigenetic-based memory systems that direct cell fate. Enzymes termed histone demethylases directly remove the methyl marks from histones, thus contributing to a dynamically regulated histone methylated genome; however, the biological functions of these newly identified enzymes remain unclear. The JMJD2A-D family belongs to the JmjC domain-containing family of histone demethylases (JHDMs). Here, we report the cloning and functional characterization of the Drosophila HDM gene Dmel\Kdm4A that is a homolog of the human JMJD2 family. We show that homologs for three human JHDM families, JHDM1, JHDM2, and JMJD2, are present in Drosophila and that each is expressed during the Drosophila lifecycle. Disruption of Dmel\Kdm4A results in a reduction of the male life span and a male-specific wing extension/twitching phenotype that occurs in response to other males and is reminiscent of an inter-male courtship phenotype involving the courtship song. Remarkably, certain genes associated with each of these phenotypes are significantly downregulated in response to Dmel\Kdm4A loss, most notably the longevity associated Hsp22 gene and the male sex-determination fruitless gene. Our results have implications for the role of the epigenetic regulator Dmel\Kdm4A in the control of genes involved in life span and male-specific sex determination in the fly.


Subject(s)
Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Epigenesis, Genetic , Gene Expression Regulation, Developmental , Histone Demethylases/metabolism , Longevity/genetics , Sex Determination Processes , Animals , Base Sequence , Drosophila Proteins/genetics , Drosophila melanogaster/enzymology , Histone Demethylases/genetics , Humans , Male , Molecular Sequence Data , Mutation , Sequence Alignment
SELECTION OF CITATIONS
SEARCH DETAIL
...