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

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

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18 Scopus citations

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

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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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