When everything is a master regulator, nothing is

The term "master regulator" emerged in the 1960s and 1970s and referred to autoregulatory transcription factors that sat atop a developmental lineage. Since that time, usage of the term has increased and broadened to the point where it has lost clear meaning. Here we discuss the term "master regulator" with the goals of developing a consensus view of its definition and stimulating discussion on use of similar terms. We propose that the designation "master regulator" be reserved for transcription factors that are: 1) positioned at the top of a regulatory hierarchy specifying a cell lineage (and potentially specific cell states, such as hypoxia); and 2) sufficient to drive the transcriptional program characterizing that lineage or state. It is hoped that this piece will provide a precedent for use of additional terms applied to incompletely understood biological processes, resulting in experimentation that sheds light on such processes.