Regulating the regulators: Lysine modifications make their mark

Decades of research have uncovered much of the molecular machinery responsible for establishing and maintaining proper gene transcription patterns in eukaryotes. Although the composition of this machinery is largely known, mechanisms regulating its activity by covalent modification are just coming into focus. Here, we review several cases of ubiquitination, sumoylation, and acetylation that link specific covalent modification of the transcriptional apparatus to their regulatory function. We propose that potential cascades of modifications serve as molecular rheostats that fine-tune the control of transcription in diverse organisms.