A Complex Array of Positive and Negative Elements Regulates the Chicken αΑ-Crystallin Gene: Involvement of Pax-6, USF, CREB and/or CREM, and AP-1 Proteins

Autor: Cvekl, A, Sax, C M, Bresnick, E H, Piatigorsky, J
Rok vydání: 1994
Předmět:
Zdroj: Molecular and Cellular Biology. 14:7363-7376
ISSN: 1098-5549
DOI: 10.1128/mcb.14.11.7363-7376.1994
Popis: The abundance of crystallins (> 80% of the soluble protein) in the ocular lens provides advantageous markers for selective gene expression during cellular differentiation. Here we show by functional and protein-DNA binding experiments that the chicken alpha A-crystallin gene is regulated by at least five control elements located at sites A (-148 to -139), B (-138 to -132), C (-128 to -101), D (-102 to -93), and E (-56 to -41). Factors interacting with these sites were characterized immunologically and by gel mobility shift experiments. The results are interpreted with the following model. Site A binds USF and is part of a composite element with site B. Site B binds CREB and/or CREM to enhance expression in the lens and binds an AP-1 complex including CREB, Fra2 and/or JunD which interacts with USF on site A to repress expression in fibroblasts. Sites C and E (which is conserved across species) bind Pax-6 in the lens to stimulate alpha A-crystallin promoter activity. These experiments provide the first direct data that Pax-6 contributes to the lens-specific expression of a crystallin gene. Site D (-104 to -93) binds USF and is a negative element. Thus, the data indicate that USF, CREB and/or CREM (or AP-1 factors), and Pax-6 bind a complex array of positive and negative cis-acting elements of the chicken alpha A-crystallin gene to control high expression in the lens and repression in fibroblasts.
Databáze: OpenAIRE