Molecular models of bidirectional promoter regulation.

Approximately 11% of human genes are transcribed by a bidirectional promoter (BDP), defined as two genes with <1 kb between their transcription start sites. Despite their evolutionary conservation and enrichment for housekeeping genes and oncogenes, the regulatory role of BDPs remains unclear. BDPs have been suggested to facilitate gene coregulation and/or decrease expression noise. This review discusses these potential regulatory functions through the context of six prospective underlying mechanistic models: a single nucleosome free region, shared transcription factor/regulator binding, cooperative negative supercoiling, bimodal histone marks, joint activation by enhancer(s), and RNA-mediated recruitment of regulators. These molecular mechanisms may act independently and/or cooperatively to facilitate the coregulation and/or decreased expression noise predicted of BDPs.