Developmentally regulated Rpd3p homolog specific to the transcriptionally active macronucleus of vegetative Tetrahymena thermophila

A clear relationship exists between histone acetylation and transcriptional output, the balance of which is conferred by opposing histone acetyltransf erases (HATs) and histone deacetylases (HDACs). To explore the role of HDAC activity in determining the transcriptional competency of chromatin, we ha ve exploited the biological features of Tetrahymena as a model. Each vegeta tive cell contains two nuclei: a somatic, transcriptionally active macronuc leus containing hyperacetylated chromatin and a transcriptionally silent, g erm line micronucleus containing hypoacetylated histones. Using a PCR-based strategy, a deacetylase gene (named THD1) encoding a homolog of the yeast HDAC Rpd3p was cloned. Thd1p deacetylates all four core histones in vitro. It resides exclusively in the macronucleus during vegetative growth and is asymmetrically distributed to developing new macronuclei early in their dif ferentiation during the sexual pathway. Together, these data are most consi stent with a potential role for Thd1p in transcriptional regulation and sug gest that histone deacetylation may be important for the differentiation of micronuclei into macronuclei during development.