Chromatin-dependent regulation of the MMTV promoter by cAMP signaling is mediated through distinct pathways

Niveen M. Mulholland, Sara K. Snyder, Sarah S. Kolla, Catharine L. Smith

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The nucleoprotein structure of the mouse mammary tumor virus (MMTV) promoter defines its response to cAMP signaling. A stably replicating MMTV template in highly organized chromatin is repressed in the presence of cAMP, whereas a transiently transfected template with a disorganized structure is activated. In this study, we investigate the nature of the cAMP-induced signal(s) by which these opposing responses occur to gain insight into their mechanism. We demonstrate that the transcriptional changes observed at both templates are mediated through cAMP-dependent protein kinase A (PKA). In addition, the MMTV promoter lacks a consensus cAMP response element (CRE) and neither template requires cAMP response element-binding protein (CREB) to elicit a response to cAMP signaling. However, the responses of the two templates differ mechanistically in that the CREB-binding protein p300 potentiates activation from the transient template in a manner dependent on its Cys/His-rich region 3, but does not appear to affect the repression of the replicating chromatin template. Chromatin immunoprecipitation assays show that cAMP treatment results in a decrease in acetylation of histone H4, and in multiple modifications of histone H3 at specific nucleosomes in the promoter region of the stable MMTV template. These findings suggest novel CREB-independent, chromatin-dependent pathways for transcriptional regulation by cAMP.

Original languageEnglish (US)
Pages (from-to)361-373
Number of pages13
JournalExperimental Cell Research
Volume287
Issue number2
DOIs
StatePublished - Jul 15 2003
Externally publishedYes

Keywords

  • Chromatin
  • Glucocorticoid receptor
  • Mouse mammary tumor virus promoter
  • Repression
  • Transcription
  • cAMP signaling

ASJC Scopus subject areas

  • Cell Biology

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