Full Paper

You have free access to this content

Live-Cell Studies of p300/CBP Histone Acetyltransferase Activity and Inhibition

  1. Beverley M. Dancy1,5,
  2. Dr. Nicholas T. Crump2,
  3. Daniel J. Peterson3,
  4. Dr. Chandrani Mukherjee1,
  5. Dr. Erin M. Bowers1,
  6. Dr. Young-Hoon Ahn1,
  7. Dr. Minoru Yoshida4,
  8. Dr. Jin Zhang1,
  9. Dr. Louis C. Mahadevan2,
  10. Dr. David J. Meyers1,
  11. Dr. Jef D. Boeke5,
  12. Dr. Philip A. Cole1,*

Article first published online: 7 SEP 2012

DOI: 10.1002/cbic.201200381

Issue

ChemBioChem

ChemBioChem

Volume 13, Issue 14, pages 2113–2121, September 24, 2012

Additional Information

How to Cite

Dancy, B. M., Crump, N. T., Peterson, D. J., Mukherjee, C., Bowers, E. M., Ahn, Y.-H., Yoshida, M., Zhang, J., Mahadevan, L. C., Meyers, D. J., Boeke, J. D. and Cole, P. A. (2012), Live-Cell Studies of p300/CBP Histone Acetyltransferase Activity and Inhibition. ChemBioChem, 13: 2113–2121. doi: 10.1002/cbic.201200381

Author Information

  1. 1

    Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 (USA)

  2. 2

    Nuclear Signalling Laboratory, Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1 3QU (UK)

  3. 3

    Laboratory for Neurocognitive and Imaging Research, Kennedy Krieger Institute, 716 North Broadway, Baltimore, MD 21205 (USA)

  4. 4

    Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan)

  5. 5

    Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205 (USA)

*Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 (USA)

Publication History

  1. Issue published online: 18 SEP 2012
  2. Article first published online: 7 SEP 2012
  3. Manuscript Received: 8 JUN 2012

Funded by

  • National Institutes of Health. Grant Numbers: U54-RR020839, GM62437, R01-DK073368

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (1424K)

Keywords:

  • drug design;
  • enzymes;
  • FRET;
  • histone H4;
  • protein modifications

Abstract

Histone acetyltransferase enzymes (HATs) are important therapeutic targets, but there are few cell-based assays available for evaluating the pharmacodynamics of HAT inhibitors. Here we present the application of a FRET-based reporter, Histac, in live-cell studies of p300/CBP HAT inhibition, by both genetic and pharmacologic disruption. shRNA knockdown of p300/CBP led to increased Histac FRET, thus suggesting a role for p300/CBP in the acetylation of the histone H4 tail. Additionally, we describe a new p300/CBP HAT inhibitor, C107, and show that it can also increase cellular Histac FRET. Taken together, these studies provide a live-cell strategy for identifying and evaluating p300/CBP inhibitors.

View Full Article with Supporting Information (HTML) Get PDF (1424K)