Histones are a class of eucharyotic genes whose expression is exquisitely controlled during cell division. This control must certainly relfect the critical role which these proteins play in a variety of cellular processes. We will first examine the mechanisms which govern histone gene expression and, then, by the isolation of conditional histone mutants, delineate the cellular functions in which histones are pivotal. We have shown that yeast histone genes are regulated both transcriptionally and post-transcriptionally. We have proposed that periodic transcription is effected by the replicative state of histone chromatin. Support for this notion has come from demonstration that ori sequences are located at the 3' ends of each H2B gene and that these sequences are necessary for transcription specificity. By in vitro mutagenesis we will delineate both the replication and regulatory sequences. We will also identify, by mutational analysis, genes which act upon this region. We have shown that post-transcriptional regulation is achieved by changes in histone mRNA half-life and is a function of the DNA replication rate. We will define the sequences responsible for theis regulation as well as identify, by mutational analysis, the proteins which interact with them. Finally, we propose three separate schemes for isolation of (ts) histone mutants as well as experiments in which these mutants can be utilized to delineate the role of histones in a number of cellular functions.
| Norris, D; Osley, M A (1987) The two gene pairs encoding H2A and H2B play different roles in the Saccharomyces cerevisiae life cycle. Mol Cell Biol 7:3473-81 |
| Osley, M A; Gould, J; Kim, S et al. (1986) Identification of sequences in a yeast histone promoter involved in periodic transcription. Cell 45:537-44 |
