Lens-specific gene recruitment of ζ-crystallin through Pax6, Nrl-Maf, and brain suppressor sites

Ronit Sharon-Friling, Jill Richardson, Sally Sperbeck, Douglas Lee, Michael Rauchman, Richard Maas, Anand Swaroop, Graeme Wistow

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32 Scopus citations

Abstract

ζ-Crystallin is a taxon-specific crystallin, an enzyme which has undergone direct gene recruitment as a structural component of the guinea pig lens through a Pax6-dependent mechanism. Tissue specificity arises through a combination of effects involving three sites in the lens promoter. The Pax6 site (ZPE) itself shows specificity for an isoform of Pax6 preferentially expressed in lens cells. High-level expression of the promoter requires a second site, identical to an αCE2 site or half Maf response element (MARE), adjacent to the Pax6 site. A promoter fragment containing Pax6 and MARE sites gives lens-preferred induction of a heterologous promoter. Complexes binding the MARE in lens nuclear extracts are antigenically related to Nrl, and cotransfection with Nrl elevates ζ-crystallin promoter activity in lens cells. A truncated ζ promoter containing Nrl-MARE and Pax6 sites has a high level of expression in lens cells in transgenic mice but is also active in the brain. Suppression of the promoter in the brain requires sequences between -498 and -385, and a site in this region forms specific complexes in brain extract. A three-level model for lens-specific Pax6-dependent expression and gene recruitment is suggested: (i) binding of a specific isoform of Pax6; (ii) augmentation of expression through binding of Nrl or a related factor; and (iii) suppression of promoter activity in the central nervous system by an upstream negative element in the brain but not in the lens.

Original languageEnglish
Pages (from-to)2067-2076
Number of pages10
JournalMolecular and cellular biology
Volume18
Issue number4
StatePublished - Apr 1 1998
Externally publishedYes

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    Sharon-Friling, R., Richardson, J., Sperbeck, S., Lee, D., Rauchman, M., Maas, R., Swaroop, A., & Wistow, G. (1998). Lens-specific gene recruitment of ζ-crystallin through Pax6, Nrl-Maf, and brain suppressor sites. Molecular and cellular biology, 18(4), 2067-2076.