Regulation of Histone Gene Expression During Drosophila Development

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

The functional building block of all eukaryotic chromosomes is a structure called the nucleosome, which is composed of a short stretch of DNA wrapped around a complex of 8 histone proteins. Many thousands of nucleosomes are needed to package a cell's entire complement of DNA into chromosomes. The proper inheritance and function of genes rely on specialized domains within the chromosomes that carry these genes. The correct assembly of nucleosomes plays a pivotal role in the establishment and maintenance of these chromosome domains, and consequently in the maintenance of a properly functioning genome. Nucleosome assembly requires coordinated, temporal control of histone protein biosynthesis. Histone production is tightly coupled to the rate of DNA replication during cell proliferation, because new nucleosomes must be formed to package the newly made DNA. The cell's ability to control the level of histone mRNA, which is translated into histone protein, accounts for nearly all of the control of histone protein biosynthesis. This control operates at many levels, including production of the mRNA, stability of the mRNA within the cell, and translation of the mRNA into protein. The goals of this project are to determine the molecular mechanisms of histone mRNA biosynthesis and metabolism, and how they are coupled to the rate of DNA replication during cell division throughout animal development. Histone mRNA metabolism is one of the best systems for exploring the multitude of strategies that eukaryotic cells use to coordinately regulate the expression of a family of mRNAs. Moreover, this research project will have an impact on scientific education. Both graduate and undergraduate students will perform the bulk of the experimental work, which provides extensive training in genetics, molecular biology, and cell biology.