Studying Transcriptional Enhancers: The Founder Fallacy, Validation Creep, and Other Biases

Abstract

Transcriptional enhancers play a major role in regulating metazoan gene expression. Recent developments in genomics and next-generation sequencing have accelerated and revitalized the study of this important class of sequence elements. Increased interest and attention, however, has also led to troubling trends in the enhancer literature. In this Opinion, I describe some of these issues and show how they arise from shifting and nonuniform enhancer definitions, and genome-era biases. I discuss how they can lead to interpretative errors and an unduly narrow focus on certain aspects of enhancer biology to the potential exclusion of others.

Keywords: bias; cis-regulatory module; enhancer; genomic assay; transcription.