An archaeal transcription factor bridges prokaryotic and eukaryotic regulatory paradigms

Archaeal transcription is a hybrid of eukaryotic and prokaryotic features: an RNA polymerase II (RNAPII)-like polymerase transcribes genes organized in circular chromosomes within cells devoid of a nucleus. Consequently, archaeal genomes are depleted of transcriptional regulators found in other domains of life. Here, we outline the discovery of a cryptic, archaea-specific family of ligand-binding regulatory transcription factors (TFs), called AmzR (archaeal metabolite-sensing zipper-like regulators). We identify AmzR using an evolution-based genetic screen and show that it is a repressor of methanogenic growth on methylamines in the archaeon Methanosarcina acetivorans. AmzR binds its target promoters as an oligomer using paired basic α-helices akin to eukaryotic leucine zippers. AmzR also binds methylamines, which reduces its DNA-binding affinity and allows it to function as a one-component system commonly found in prokaryotes, while containing a eukaryotic-like DNA-binding motif. The AmzR family of TFs are widespread in archaea and broaden the scope of innovations at the prokaryote-eukaryote interface.