title: SET and PARP1 remove DEK from chromatin to permit access by the transcription machinery.
abstract: 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.
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, New York 10021, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gamble
authors.forename: Robert P
authors.initials: RP
authors.lastname: Fisher
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D056488:Histone Chaperones; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C084738:DEK protein, human; D056488:Histone Chaperones; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C513473:SET protein, human; D014157:Transcription Factors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D012319:RNA Polymerase II