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PMID: 9528779 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 18 ·No. 4 ·1998-04-00 ·Pages 2067-76

Sharon-Friling R, Richardson J, Sperbeck S, Lee D, Rauchman M, Maas R, Swaroop A, Wistow G

Abstract

Zeta-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 alphaCE2 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 zeta-crystallin promoter activity in lens cells. A truncated zeta 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.

MeSH Terms
Animals Base Sequence Basic-Leucine Zipper Transcription Factors Cells, Cultured Consensus Sequence Crystallins/genetics,metabolism DNA-Binding Proteins/metabolism Eye Proteins/metabolism Homeodomain Proteins Lens, Crystalline/metabolism Leucine Zippers Maf Transcription Factors Mice Mice, Transgenic Molecular Sequence Data PAX6 Transcription Factor Paired Box Transcription Factors Rabbits Repressor Proteins Transcription Factors/metabolism
Chemicals
Basic-Leucine Zipper Transcription Factors Crystallins DNA-Binding Proteins Eye Proteins Homeodomain Proteins L-MAF protein, Gallus gallus Maf Transcription Factors Nrl protein, mouse PAX6 Transcription Factor Paired Box Transcription Factors Pax6 protein, mouse Repressor Proteins Transcription Factors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Sharon-Friling R
Section on Molecular Structure and Function, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Richardson J
Sperbeck S
Lee D
Rauchman M
Maas R
Swaroop A
Wistow G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.4.2067
Published
1998-04-00
Pages
2067-76
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC121437
Subset
IM
Grants
NEI NIH HHS · EY01115 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.4.2067 PMC Full Text View journal details
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