Regulation of c-Maf and αA-Crystallin in ocular lens by fibroblast growth factor signaling

Qing Xie, Rebecca McGreal, Raven Harris, Chun Y. Gao, Wei Liu, Lixing W. Reneker, Linda Musil, Ales Cvekl

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Fibroblast growth factor (FGF) signaling regulates a multitude of cellular processes, including cell proliferation, survival, migration, and differentiation. In the vertebrate lens, FGF signaling regulates fiber cell differentiation characterized by high expression of crystallin proteins. However, a direct link between FGF signaling and crystallin gene transcriptional machinery remains to be established. Previously, we have shown that the bZIP proto-oncogene c-Maf regulates expression of αA-crystallin (Cryaa) through binding to its promoter and distal enhancer, DCR1, both activated by FGF2 in cell culture. Herein, we identified and characterized a novel FGF2-responsive region in the c-Maf promoter (-272/-70, FRE). Both c-Maf and Cryaa regulatory regions contain arrays of AP-1 and Ets-binding sites. Chromatin immunoprecipitation (ChIP) assays established binding of c-Jun (an AP-1 factor) and Etv5/ERM (an Ets factor) to these regions in lens chromatin. Analysis of temporal and spatial expression of c-Jun, phospho-c-Jun, and Etv5/ERM in wild type and ERK1/2 deficient lenses supports their roles as nuclear effectors of FGF signaling in mouse embryonic lens. Collectively, these studies show that FGF signaling up-regulates expression of αA-crystallin both directly and indirectly via upregulation of c-Maf. These molecular mechanisms are applicable for other crystallins and genes highly expressed in terminally differentiated lens fibers.

Original languageEnglish (US)
Pages (from-to)3947-3958
Number of pages12
JournalJournal of Biological Chemistry
Volume291
Issue number8
DOIs
StatePublished - Feb 19 2016

Fingerprint

Crystalline Lens
Crystallins
Fibroblast Growth Factors
Lenses
Transcription Factor AP-1
Fibroblast Growth Factor 2
Chromatin
Up-Regulation
Genes
Spatio-Temporal Analysis
Proto-Oncogenes
Fibers
Chromatin Immunoprecipitation
Nucleic Acid Regulatory Sequences
Cell proliferation
Cell culture
Machinery
Vertebrates
Cell Differentiation
Assays

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Molecular Biology
  • Cell Biology

Cite this

Xie, Q., McGreal, R., Harris, R., Gao, C. Y., Liu, W., Reneker, L. W., ... Cvekl, A. (2016). Regulation of c-Maf and αA-Crystallin in ocular lens by fibroblast growth factor signaling. Journal of Biological Chemistry, 291(8), 3947-3958. https://doi.org/10.1074/jbc.M115.705103

Regulation of c-Maf and αA-Crystallin in ocular lens by fibroblast growth factor signaling. / Xie, Qing; McGreal, Rebecca; Harris, Raven; Gao, Chun Y.; Liu, Wei; Reneker, Lixing W.; Musil, Linda; Cvekl, Ales.

In: Journal of Biological Chemistry, Vol. 291, No. 8, 19.02.2016, p. 3947-3958.

Research output: Contribution to journalArticle

Xie, Q, McGreal, R, Harris, R, Gao, CY, Liu, W, Reneker, LW, Musil, L & Cvekl, A 2016, 'Regulation of c-Maf and αA-Crystallin in ocular lens by fibroblast growth factor signaling', Journal of Biological Chemistry, vol. 291, no. 8, pp. 3947-3958. https://doi.org/10.1074/jbc.M115.705103
Xie, Qing ; McGreal, Rebecca ; Harris, Raven ; Gao, Chun Y. ; Liu, Wei ; Reneker, Lixing W. ; Musil, Linda ; Cvekl, Ales. / Regulation of c-Maf and αA-Crystallin in ocular lens by fibroblast growth factor signaling. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 8. pp. 3947-3958.
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