Position Effects

Abstract

Position effects describe the observed alteration in protein-coding gene expression that may accompany a change in genomic position of a given gene. A position effect may result from chromosomal translocation or other genomic rearrangements. Recent advances in chromatin studies in several different species including yeast, Drosophila, and mouse have contributed significantly to better understanding of human diseases resulting from abnormal epigenetic effects. Molecular models attempting to explain position effects in humans have been proposed; however, none of them adequately addresses a variety of mechanisms. According to the noncontact models, the cis- or trans-regulatory elements, or locus control regions, are physically separated from the target gene and act either at the RNA level, by protein interactions, or by mediation of boundary elements, termed insulators. On the contrary, the contact models invoke spatial-temporal modifications of chromatin structure (e.g., active chromatin hub). In both models, the conserved nongenic sequences (CNGs) may play an important role in genomic regulation of gene expression. The recent introduction of new techniques including tagging and recovery of associated proteins (RNA-TRAP) and capturing chromatin conformation (CCC or 3C), has provided powerful tools to investigate position effects in humans.