Follicle-stimulating Hormone Stimulates Protein Kinase A-mediated Histone H3 Phosphorylation and Acetylation Leading to Select Gene Activation in Ovarian Granulosa Cells

Lisa M. Salvador, Youngkyu Park, Joshua Cottom, Evelyn T. Maizels, Jonathan C.R. Jones, Robynn V. Schillace, Daniel W. Carr, Peter Cheung, C. David Allis, J. Larry Jameson, Mary Hunzicker-Dunn

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

We examined the phosphorylation and acetylation of histone H3 in ovarian granulosa cells stimulated to differentiate by follicle-stimulating hormone (FSH). We found that protein kinase A (PKA) mediates H3 phosphorylation on serine 10, based on inhibition exclusively by PKA inhibitors. FSH-stimulated H3 phosphorylation in granulosa cells is not downstream of mitogen-activated protein kinase/extracellular signal-regulated kinase, ribosomal S6 kinase-2, mitogen- and stress-activated protein kinase-1, p38 MAPK, phosphatidylinositol-3 kinase, or protein kinase C. Transcriptional activation-associated H3 phosphorylation on serine 10 and acetylation of lysine 14 leads to activation of serum glucocorticoid kinase, inhibin α, and c-fos genes. We propose that phosphorylation of histone H3 on serine 10 by PKA in coordination with acetylation of H3 on lysine 14 results in reorganization of the promoters of select FSH responsive genes into a more accessible configuration for activation. The unique role of PKA as the physiological histone H3 kinase is consistent with the central role of PKA in initiating granulosa cell differentiation.

Original languageEnglish (US)
Pages (from-to)40146-40155
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number43
DOIs
StatePublished - Oct 26 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Follicle-stimulating Hormone Stimulates Protein Kinase A-mediated Histone H3 Phosphorylation and Acetylation Leading to Select Gene Activation in Ovarian Granulosa Cells'. Together they form a unique fingerprint.

  • Cite this

    Salvador, L. M., Park, Y., Cottom, J., Maizels, E. T., Jones, J. C. R., Schillace, R. V., Carr, D. W., Cheung, P., Allis, C. D., Jameson, J. L., & Hunzicker-Dunn, M. (2001). Follicle-stimulating Hormone Stimulates Protein Kinase A-mediated Histone H3 Phosphorylation and Acetylation Leading to Select Gene Activation in Ovarian Granulosa Cells. Journal of Biological Chemistry, 276(43), 40146-40155. https://doi.org/10.1074/jbc.M106710200