Since the discovery of the SUMO (small ubiquitin-related modifier) family of proteins just over a decade ago, a plethora of substrates have been uncovered including many regulators of transcription. Conjugation of SUMO to target proteins has generally been considered as a repressive modification. However, there are now a growing number of examples where SUMOylation has been shown to activate transcription. Here, we discuss whether there is something intrinsically repressive about SUMOylation, or if the outcome of this modification in the context of transcription will prove to be largely substrate-dependent. We highlight some of the technical challenges that will be faced by attempting to answer this question.

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