Histone deacetylases regulate multicellular development in the social amoeba Dictyostelium discoideum.
Epigenetic modifications of histones regulate gene expression and lead to the establishment and maintenance of cellular phenotypes during development. Histone acetylation depends on a balance between the activities of histone acetyltransferases and histone deacetylases (HDACs) and influences transcriptional regulation. In this study, we analyse the roles of HDACs during growth and development of one of the cellular slime moulds, the social amoeba Dictyostelium discoideum. The inhibition of HDAC activity by trichostatin A results in histone hyperacetylation and a delay in cell aggregation and differentiation. Cyclic AMP oscillations are normal in starved amoebae treated with trichostatin A but the expression of a subset of cAMP-regulated genes is delayed. Bioinformatic analysis indicates that there are four genes encoding putative HDACs in D. discoideum. Using biochemical, genetic and developmental approaches, we demonstrate that one of these four genes, hdaB, is dispensable for growth and development under laboratory conditions. A knockout of the hdaB gene results in a social context-dependent phenotype: hdaB(-) cells develop normally but sporulate less efficiently than the wild type in chimeras. We infer that HDAC activity is important for regulating the timing of gene expression during the development of D. discoideum and for defining aspects of the phenotype that mediate social behaviour in genetically heterogeneous groups.
Sawarkar
Ritwick
R
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India. ritwick@mrdg.iisc.ernet.in
Visweswariah
Sandhya S
SS
Nellen
Wolfgang
W
Nanjundiah
Vidyanand
V
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D015800:Protozoan Proteins; C012589:trichostatin A; D000242:Cyclic AMP; D006655:Histone Deacetylases