Research emphasizes the role of chromatin in gene expression. The model system involves the macro-and micronuclei of the ciliate, Tetrahymena thermophila which present a unique opportunity to study the mechanisms by which the same genetic information differntiates and is maintained in different states. These two nuclei occupy the same cytoplasm but differ markedly in structure and function. The germline micronuclei divide mitotically and are transcriptionally inert. The somatic macronuclei divide amitotically and are transcriptionally active. Two multi-gene families are under investigation: histone genes and tubulin genes. Methods for mass transformation and gene replacement have been developed that allow analyses in vivo using gene knockouts and gene replacement and creation of transgenic strains. These techniques are being used to study evolutionally conserved aspects of these two multigene families. Current studies on the histone multigene family include determining the function of the linker histone H1 in chromosome condensation and transcription, the function of histone H2A and H3 variants in transcription and the function of histone phosphorylation and acetylation. Studies on the tubulin genes include analyses of the role of specific tubulin genes and their secondary modifications in generating the diverse functions of microtubules and studies on the mechanisms regulating tubulin gene expression.