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

Nat Struct Mol Biol. 2007 Jun;14(6):548-55. doi: 10.1038/nsmb1248. Epub 2007 May 27.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins
  • HeLa Cells
  • Histone Chaperones
  • Humans
  • Oncogene Proteins / metabolism*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Poly-ADP-Ribose Binding Proteins
  • RNA Polymerase II / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic / genetics
  • Transcription, Genetic / physiology*

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Dek protein, human
  • Histone Chaperones
  • Oncogene Proteins
  • Poly-ADP-Ribose Binding Proteins
  • SET protein, human
  • Transcription Factors
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • RNA Polymerase II