A gene's chromosomal position and local chromatin context can have profound consequences for its expression. We are interested in all aspects of this problem, described as position-effect gene regulation , and have been studying it in yeast. We are particularly interested in the form of this regulation known as silencing, or position-specific transcriptional repression. Our experimental approaches are strongly influenced by the wealth of genetic and molecular data that have accumulated from experiments in yeast, Drosophila and vertebrates.
Many genes influence silencing in yeast.
Several of these genes are known to function in structural aspects of nuclear organization as well as having effects on transcription. In particular, we are analyzing the roles of Sir3p and Sir4p in telomere structure, function and transcription. We have discovered that Sir3p is subject to regulated phosphorylation events that may influence its function. Sir2p and three newly discovered SAS genes in silencing and nuclear organization. The SAS genes of the MYST family are particularly interesting because they are very similar to human genes associated with an acute myeloid leukemia and with HIV-1 Tat interactions and to a Drosophila gene essential for dosage compensation in males.