Telokin expression in A10 smooth muscle cells requires serum response factor

Am J Physiol. 1997 Apr;272(4 Pt 1):C1394-404. doi: 10.1152/ajpcell.1997.272.4.C1394.

Abstract

Telokin transcription is initiated from a smooth muscle-specific promoter located in an intron of the smooth muscle myosin light chain kinase gene. We have previously identified a 310-base pair fragment of the promoter that mediates A10 smooth muscle cell-specific expression of telokin. In the current study, telokin-luciferase reporter gene assays in A10 cells and REF52 nonmuscle cells revealed that the promoter region between -81 and +80 contains the regulatory elements required to mediate the in vitro cell specificity of the promoter. Several positive-acting elements, including an E box, myocyte enhancer factor 2 (MEF2)-TATA box, and CArG-serum response element, were identified within this region. Telokin transcription in A10 smooth muscle cells requires all three transcription initiation sites and an AT-rich sequence between -71 and -62 that includes a TATA box. MEF2 interacts with the AT-rich region with low affinity; however, MEF2 binding is not required for transcriptional activity in A10 cells. Binding of serum response factor (SRF) to a CArG element proximal to the TATA sequence is also critical for high levels of transcription in A10 cells. Together these data suggest that an AT-rich motif, acting in concert with SRF and an unusual transcription initiation mechanism, is required for the cell-specific expression of the telokin promoter in A10 smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation*
  • MEF2 Transcription Factors
  • Molecular Sequence Data
  • Muscle Proteins / genetics*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / physiology*
  • Myogenic Regulatory Factors
  • Myosin-Light-Chain Kinase
  • Nuclear Proteins / physiology*
  • Peptide Fragments
  • Peptides
  • Promoter Regions, Genetic
  • Rats
  • Serum Response Factor
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • MEF2 Transcription Factors
  • Muscle Proteins
  • Myogenic Regulatory Factors
  • Nuclear Proteins
  • Peptide Fragments
  • Peptides
  • Serum Response Factor
  • Transcription Factors
  • telokin
  • Myosin-Light-Chain Kinase