Involvement of multiple cis elements in basal- and α-adrenergic agonist- inducible atrial natriuretic factor transcription: Roles for serum response elements and an SP-1-like element

A. B. Sprenkle, S. F. Murray, C. C. Glembotski

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

In the present study, cis elements in the 5'-flanking sequence (FS) of the rat atrial natriuretic factor (ANF) gene involved in regulating basal and α1-adrenergic-inducible transcription were investigated. Truncation analyses using ANF-luciferase reporter constructs transfected into primary neonatal rat cardiac myocytes showed that an A/T-rich serum response element (SRE) at -114 bp of the ANF 5'-FS, which bound serum response factor (SRF), was required for basal anti inducible transcription. In constructs composed of 134 bp of rat ANF 5'-FS driving luciferase (ANF-134Luc), mutations in the SRE at -114 bp disrupted SRF binding and ANF promoter activity. However, the same mutations in ANF-638Luc had little effect, suggesting a collaborating role for more distal sequences, such as the other SRE in ANF-638 at -406 bp. In ANF-638Luc, mutations in the SRE at -406 bp that disrupted SRF binding to that silo decreased ANF reporter activity by only 25%; however, mutating both of the SREs completely blocked α1-adrenergic-inducible activity. Mutation analyses showed that an ··· (SP-1)-like site at -66 bp, shown previously to confer inducibility in reporters with 134 bp of ANF 5'-FS, was not required in ANF-638Luc. However, double mutants in the SP-1 like region and either SRE completely blocked α1-adrenergic-inducible ANF promoter activity. These findings emphasize that no single element is responsible for α1-adrenergic agonist-regulated ANF transcription but thai the SREs at -114 and -406 bp and the SP-1-like sequence at -69 bp mediate the effect in collaboration.

Original languageEnglish (US)
Pages (from-to)1060-1069
Number of pages10
JournalCirculation research
Volume77
Issue number6
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • atrial natriuretic factor
  • serum response element
  • serum response factor
  • transcription
  • α-adrenergic agonist inducibility

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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