Epigenetic Control of Gene Expression

Genetic mutations lead to inheritable changes in the traits. Alterations in genetic features may also be caused by chromatin modifications without any changes in DNA. Such epigenetic phenomena play increasingly critical roles in regulating gene expression in most cellular and developmental events. This chapter focuses on the genetic identification of epigenetic regulators of gene expression. Position-effect variegationPosition-effect-variegation (PEVPEV) is a well-known epigenetic phenomenon affecting gene expression by altering a gene’s chromatin environment through chromosomal rearrangements. PEV was extensively studied in Drosophila long before histone acetyltransferase was discovered as a landmark epigenetic regulator. Firstly, we will discuss how PEV was used to identify epigenetic regulators, including histone methyltransferases and acetylases. Secondly, we will discuss Polycomb and Trithorax group genes. These genes, initially found as regulators of homeotic genes in Drosophila development, provide distinct protein complexes for epigenetic regulation of gene expression. Lastly, we will discuss a genetic approach to finding epigenetic regulators in the mouse. Like PEV, a transgene expression can be affected by the epigenetic conditions of mammalian cells. We will examine how transgenic PEV can be used for isolating new mammalian PEV modifier mutations. These studies illustrate that genetic applications of PEV in model organisms facilitate the identification of epigenetic regulators of gene expression.