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

Nature Structural & Molecular Biology volume 14, pages 548–555 (2007)Cite this article

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.

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Figure 1: SET and NAD+ have similar effects on chromatin structure and function.
Figure 2: Purification of DEK as a repressor of nuclease accessibility.
Figure 3: DEK mediates SET-sensitive repression of chromatin accessibility and transcription.
Figure 4: DEK is a target for poly(ADP-ribosyl)ation by PARP1.
Figure 5: SET and poly(ADP-ribosyl)ation promote dissociation of DEK and PARP1 from chromatin.
Figure 6: SET or NAD+ is required for loading Mediator.

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Acknowledgements

We thank S. Larochelle and J. Lis (Cornell University) for critical review of the manuscript and for many helpful discussions; W. Lee Kraus (Cornell University) for helpful comments and suggestions, for PARP1 and Gal4-VP16 expression vectors and pGEIO plasmid, and for material support during the revision process; H. Erdjument-Bromage and P. Tempst for mass spectrometric identification of DEK, SET and PARP1; T. Ito (Nagasaki University) for core histone–specific antibodies; J. Kadonaga (University of California, San Diego) for NAP1, ISWI and Acf1 baculoviruses; M. Ptashne for Gal4 DNA-binding domain–specific antibodies; and R. Roeder (Rockefeller University) for MED30-specific antibodies. HeLa cells were provided by the National Cell Culture Center (US). This work was supported in part by US National Institutes of Health grant DK45460 to R.P.F.

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  1. Matthew J Gamble

    Present address: Present address: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.,

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  1. Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, 10021, New York, USA

    Matthew J Gamble & Robert P Fisher

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M.J.G. designed and executed experiments and prepared the manuscript; R.P.F. prepared the manuscript.

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Correspondence to Robert P Fisher.

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Supplementary information

Supplementary Fig. 1

Time course of restriction endonuclease accessibility of chromatin in the presence of SET and/or the PC1 fraction. (PDF 78 kb)

Supplementary Fig. 2

Removal of DEK is not sufficient to restore chromatin transcription of PIC assembly in the absence of SET. (PDF 557 kb)

Supplementary Fig. 3

GST or thrombin does not affect chromatin transcription. (PDF 390 kb)

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Gamble, M., Fisher, R. SET and PARP1 remove DEK from chromatin to permit access by the transcription machinery. Nat Struct Mol Biol 14, 548–555 (2007). https://doi.org/10.1038/nsmb1248

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