Paramutation: Epigenetic Instructions Passed Across Generations

Abstract

PARAMUTATION is the fascinating ability of specific DNA sequences to communicate in trans to establish meiotically heritable expression states. Intriguingly, newly silenced sequences continue to issue instructions to naive alleles in subsequent generations. The term “paramutation” was first coined in the 1950s by Alexander Brink to describe this puzzling phenomenon at the r1 locus in maize (Brink 1956); an interaction between specific alleles in heterozygotes led to heritable decreases in gene expression of one allele. Not only was the reduced expression state stable through meiosis, but also the low-expressing allele could induce silencing of another high-expressing allele in subsequent generations. The frequency of the change was 100% and the stability of the change was lower than typical mutations; hence the term “paramutation.” A few years later, Ed Coe, Jr., described another maize example in which interaction between alleles at the b1 locus also led to heritable silencing (Coe 1959) and Rudolf Hagemann described interactions at the sulfurea locus in tomato (Hagemann 1969). Since that time other examples of paramutation have been identified in maize and in other species (reviewed in Chandler and Stam 2004; Stam and Mittelsten Scheid 2005; Chandler 2007), yet the two maize loci where paramutation was initially described, r1 and b1, remain the most extensively characterized and best understood. The r1 and b1 loci encode closely related, functionally equivalent transcription factors that activate the anthocyanin pigment biosynthetic pathway (Goff et al. 1990; Ludwig et al. 1990). They are likely related to each other through a duplication resulting from an ancient allotetraploidization event during maize evolution (Gaut and Doebley 1997). The two loci have multiple alleles with distinct expression patterns, which regulate the distribution of anthocyanin pigments during development (Styles et al. 1973; Coe 1979). Recent work demonstrates a key role for RNA in mediating both r1 and b1 paramutation, as the mop1 gene that encodes an RNA-dependent RNA polymerase (RDR; Alleman et al. 2006) is absolutely required for paramutation at both loci (Dorweiler et al. 2000). Yet, there are striking differences in the properties of r1 and b1 paramutation, which hint at distinct mechanisms. In this article, the most striking differences between r1 and b1 paramutation are described and potential mechanisms are discussed relative to our current understanding of the role of RNA interference (RNAi) in mediating transcriptional silencing.