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

Beverley M. Dancy; Nicholas T. Crump; Daniel J. Peterson; Chandrani Mukherjee; Erin M. Bowers; Young Hoon Ahn; Minoru Yoshida; Jin Zhang; Louis C. Mahadevan; David J. Meyers; Jef D. Boeke; Philip A. Cole

doi:10.1002/cbic.201200381

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

Beverley M. Dancy, Nicholas T. Crump, Daniel J. Peterson, Chandrani Mukherjee, Erin M. Bowers, Young Hoon Ahn, Minoru Yoshida, Jin Zhang, Louis C. Mahadevan, David J. Meyers, Jef D. Boeke, Philip A. Cole

School of Medicine

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2113-2121
Number of pages	9
Journal	ChemBioChem
Volume	13
Issue number	14
DOIs	https://doi.org/10.1002/cbic.201200381
State	Published - Sep 24 2012

Keywords

Drug design
Enzymes
FRET
Histone H4
Protein modifications

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Organic Chemistry

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10.1002/cbic.201200381

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title = "Live-Cell Studies of p300/CBP Histone Acetyltransferase Activity and Inhibition",

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.",

keywords = "Drug design, Enzymes, FRET, Histone H4, Protein modifications",

author = "Dancy, {Beverley M.} and Crump, {Nicholas T.} and Peterson, {Daniel J.} and Chandrani Mukherjee and Bowers, {Erin M.} and Ahn, {Young Hoon} and Minoru Yoshida and Jin Zhang and Mahadevan, {Louis C.} and Meyers, {David J.} and Boeke, {Jef D.} and Cole, {Philip A.}",

year = "2012",

month = sep,

day = "24",

doi = "10.1002/cbic.201200381",

language = "English (US)",

volume = "13",

pages = "2113--2121",

journal = "ChemBioChem",

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T1 - Live-Cell Studies of p300/CBP Histone Acetyltransferase Activity and Inhibition

AU - Dancy, Beverley M.

AU - Crump, Nicholas T.

AU - Peterson, Daniel J.

AU - Mukherjee, Chandrani

AU - Bowers, Erin M.

AU - Ahn, Young Hoon

AU - Yoshida, Minoru

AU - Zhang, Jin

AU - Mahadevan, Louis C.

AU - Meyers, David J.

AU - Boeke, Jef D.

AU - Cole, Philip A.

PY - 2012/9/24

Y1 - 2012/9/24

N2 - 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.

AB - 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.

KW - Drug design

KW - Enzymes

KW - FRET

KW - Histone H4

KW - Protein modifications

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AN - SCOPUS:84866465308

SN - 1439-4227

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JO - ChemBioChem

JF - ChemBioChem

IS - 14

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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