Regulation of αA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin

Ying Yang, Tomáš Stopka, Nady Golestaneh, Yan Wang, Kongming Wu, Anping Li, Bharesh K. Chauhan, Chun Y. Gao, Květa Cveklová, Melinda K. Duncan, Richard G. Pestell, Ana B. Chepelinsky, Arthur I. Skoultchi, Aleš Cvekl

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Pax6 and c-Maf regulate multiple stages of mammalian lens development. Here, we identified novel distal control regions (DCRs) of the αA-crystallin gene, a marker of lens fiber cell differentiation induced by FGF-signaling. DCR1 stimulated reporter gene expression in primary lens explants treated with FGF2 linking FGF-signaling with αA-crystallin synthesis. A DCR1/αA-crystallin promoter (including DCR2) coupled with EGFP virtually recapitulated the expression pattern of αA-crystallin in lens epithelium and fibers. In contrast, the DCR3/αA/EGFP reporter was expressed only in 'late' lens fibers. Chromatin immunoprecipitations showed binding of Pax6 to DCR1 and the αA-crystallin promoter in lens chromatin and demonstrated that high levels of αA-crystallin expression correlate with increased binding of c-Maf and CREB to the promoter and of CREB to DCR3, a broad domain of histone H3K9-hyperacetylation extending from DCR1 to DCR3, and increased abundance of chromatin remodeling enzymes Brg1 and Snf2h at the αA-crystallin locus. Our data demonstrate a novel mechanism of Pax6, c-Maf and CREB function, through regulation of chromatin-remodeling enzymes, and suggest a multistage model for the activation of αA-crystallin during lens differentiation.

Original languageEnglish (US)
Pages (from-to)2107-2118
Number of pages12
JournalEMBO Journal
Volume25
Issue number10
DOIs
StatePublished - May 17 2006

Keywords

  • Chromatin remodeling
  • Histone acetylation and methylation
  • Lens differentiation
  • Pax6
  • c-Maf

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Yang, Y., Stopka, T., Golestaneh, N., Wang, Y., Wu, K., Li, A., Chauhan, B. K., Gao, C. Y., Cveklová, K., Duncan, M. K., Pestell, R. G., Chepelinsky, A. B., Skoultchi, A. I., & Cvekl, A. (2006). Regulation of αA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin. EMBO Journal, 25(10), 2107-2118. https://doi.org/10.1038/sj.emboj.7601114