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Negative regulation of gamma-globin gene expression by cyclic AMP-dependent pathway in erythroid cells

Akio Inoue1, Yuichi Kuroyanagi, Kiminori Terui

  • 1Laboratory of Molecular Hematology, Center for Human Genetics, Boston University School of Medicine, Boston, Mass. 02118-2394, USA.

Experimental Hematology
|March 9, 2004
PubMed

Insights

The cyclic AMP (cAMP)-dependent pathway negatively regulates fetal hemoglobin (gamma-globin) gene expression in K562 cells. This pathway

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Fetal hemoglobin inducers activate the cyclic GMP (cGMP)-dependent pathway to stimulate gamma-globin gene expression.
  • The cyclic AMP (cAMP)-dependent pathway's role in gamma-globin gene expression is unknown.
  • cGMP activates the cAMP-dependent pathway by inhibiting phosphodiesterase 3 (PDE3).

Purpose of the Study:

  • To investigate the effect of the cAMP-dependent pathway on gamma-globin gene expression.
  • To determine if the cAMP-dependent pathway influences gamma-globin gene transcription.
  • To explore the relationship between cAMP, cGMP, and gamma-globin regulation.

Main Methods:

  • K562 cells were treated with forskolin to activate the cAMP-dependent pathway.
  • Gamma-globin mRNA expression was quantified using primer extension assays.
  • Gamma-globin gene promoter activity was assessed via reporter gene assays.

Main Results:

  • Phosphodiesterase 3 (PDE3) is highly expressed in K562 cells.
  • Activating the cAMP-dependent pathway inhibited hemin-induced gamma-globin mRNA expression.
  • Transcriptional activity of the gamma-globin gene promoter was reduced by cAMP pathway activation.
  • Mitogen-activated protein kinase (MAPK) phosphorylation levels remained unaffected.

Conclusions:

  • The cAMP-dependent pathway negatively regulates gamma-globin gene expression independently of MAPK pathways in K562 cells.
  • cAMP and cGMP likely have distinct roles in regulating gamma-globin gene expression in erythroid cells.
Abstract

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