48 Histones: Regulators of Transcription in Yeast

Abstract

OVERVIEW
Histones fold DNA and block initiation of transcription in vitro. Recent evidence suggests that they also regulate transcription in the living cell (Saccharomyces cerevisiae). We describe genetic studies of yeast histones that show that nucleosome loss is not merely a result, but also a cause, of transcription initiation in vivo. This suggests a model in which activator proteins must first stimulate nucleosome displacement or a change in nucleosome structure prior to full activation of the preinitiation complex. However, the nucleosome is more than just a general repressor of initiation. Core histones contain basic, flexible amino-terminal tails that have a number of unique regulatory functions. For example, different domains at the histone H4 amino terminus are responsible for repression of the yeast silent mating loci (HML and HMR) and for activation of a number of regulated genes, including GAL1 and PH05. The extreme evolutionary conservation of this histone suggests similar functions in other, more complex, eukaryotes.

INTRODUCTION
The positively charged histone proteins allow the folding of a long, negatively charged DNA polymer in a confined nuclear compartment. Aside from this reasonably well understood structural role, the question arises as to whether histones also have a regulatory role, influencing functions dependent on the folding of DNA. Such functions might include chromosomal segregation during mitosis and meiosis, replication, and transcription. This chapter concentrates largely on the approaches our laboratory has taken to the problem of histone function using the unique genetic and biochemical manipulations possible in the budding yeast, S. cerevisiae.

Nucleosome...