Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

The phosphorylation status of a cyclic AMP-responsive activator is modulated via a chromatin-dependent mechanism

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Michael, L. F.
  • Asahara, Hiroshi
  • Shulman, A. I.
  • Kraus, W. L.
  • Montminy, M.

publication date

  • 2000

journal

  • Molecular and Cellular Biology  Journal

abstract

  • Cyclic AMP (cAMP) stimulates the expression of numerous genes via the protein kinase A (PKA)-mediated phosphorylation of CREB at Ser133. Ser133 phosphorylation, in turn, promotes recruitment of the coactivator CREB binding protein and its paralog p300, histone acetyltransferases (HATs) that have been proposed to mediate target gene activation, in part, by destabilizing promoter bound nucleosomes and thereby allowing assembly of the transcriptional apparatus. Here we show that although histone deacetylase (HDAC) inhibitors potentiate target gene activation via cAMP, they do not stimulate transcription over the early burst phase, during which CREB phosphorylation and CBP/p300 recruitment are maximal. Rather, HDAC inhibitors augment CREB activity during the late attenuation phase by prolonging CREB phosphorylation on chromosomal but, remarkably, not on extrachromosomal templates. In reconstitution studies, assembly of periodic nucleosomal arrays on a cAMP-responsive promoter template potently inhibited CREB phosphorylation by PKA, and acetylation of these template-bound nucleosomes by p300 partially rescued CREB phosphorylation by PKA. Our results suggest a novel regulatory mechanism by which cellular HATs and HDACs modulate the phosphorylation status of nuclear activators in response to cellular signals.

subject areas

  • 3T3 Cells
  • Animals
  • Chromatin
  • Cyclic AMP
  • Cyclic AMP Response Element-Binding Protein
  • Cyclic AMP-Dependent Protein Kinases
  • Mice
  • Phosphorylation
  • Signal Transduction
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.20.5.1596-1603.2000

PubMed ID

  • 10669737
scroll to property group menus

Additional Document Info

start page

  • 1596

end page

  • 1603

volume

  • 20

issue

  • 5

©2019 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support