SET and PARP1 remove DEK from chromatin to permit access by the transcription machinery.

The histone chaperone SET is required for transcription of chromatin templates by RNA polymerase Pol II (Pol II) in vitro. Here we uncover a positive role for SET in dislodging DEK and PARP1, which restrict access to chromatin in the absence of SET and the PARP1 substrate NAD(+). SET binds chromatin, dissociating DEK and PARP1 to allow transcription in the absence of NAD(+). In the absence of SET, depletion of DEK restores chromatin accessibility to endonuclease but does not permit Mediator recruitment or transcription. In the presence of NAD(+), PARP1 poly(ADP-ribosyl)ates and evicts DEK (and itself) from chromatin to permit Mediator loading and transcription independent of SET. An artificial DEK variant resistant to SET and PARP1 represses transcription, indicating a requirement for DEK removal. Therefore, SET, DEK and PARP1 constitute a network governing access to chromatin by the transcription machinery.