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Retinoblastoma protein recruits histone deacetylase to repress transcription

Author

Listed:
  • Alexander Brehm

    (University of Cambridge)

  • Eric A. Miska

    (University of Cambridge)

  • Dennis J. McCance

    (University of Cambridge
    University of Rochester)

  • Juliet L. Reid

    (University of Cambridge)

  • Andrew J. Bannister

    (University of Cambridge)

  • Tony Kouzarides

    (University of Cambridge)

Abstract

The retinoblastoma protein (Rb) silences specific genes that are active in the S phase of the cell cycle and which are regulated by E2F transcription factors1. Rb binds to the activation domain of E2F and then actively represses the promoter by a mechanism that is poorly understood2,3. Here we show that Rb associates with a histone deacetylase, HDAC1, through the Rb ‘pocket’ domain. Association with the deacetylase is reduced by naturally occurring mutations in the pocket and by binding of the human papilloma virus oncoprotein E7. We find that Rb can recruit histone deacetylase to E2F and that Rb cooperates with HDAC1 to repress the E2F-regulated promoter of the gene encoding the cell-cycle protein cyclin E. Inhibition of histone deacetylase activity by trichostatin A (TSA) inhibits Rb-mediated repression of a chromosomally integrated E2F-regulated promoter. Our results indicate that histone deacetylases are important for regulating the cell cycle and that active transcriptional repression by Rb may involve the modification of chromatin structure.

Suggested Citation

  • Alexander Brehm & Eric A. Miska & Dennis J. McCance & Juliet L. Reid & Andrew J. Bannister & Tony Kouzarides, 1998. "Retinoblastoma protein recruits histone deacetylase to repress transcription," Nature, Nature, vol. 391(6667), pages 597-601, February.
    • Handle: RePEc:nat:nature:v:391:y:1998:i:6667:d:10.1038_35404
    DOI: 10.1038/35404
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    Cited by:

    1. Alison K. Barrett & Manisha R. Shingare & Andreas Rechtsteiner & Kelsie M. Rodriguez & Quynh N. Le & Tilini U. Wijeratne & Corbin E. Mitchell & Miles W. Membreno & Seth M. Rubin & Gerd A. Müller, 2024. "HDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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