TY - JOUR
T1 - A complex array of positive and negative elements regulates the chicken αA-crystallin gene
T2 - Involvement of Pax-6, USF, CREB and/or CREM, and AP-1 proteins
AU - Cvekl, Aleš
AU - Sax, Christina M.
AU - Bresnick, Emery H.
AU - Piatigorsky, Joram
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1994/11
Y1 - 1994/11
N2 - 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 αA-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 αA-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 αA-crystallin gene to control high expression in the lens and repression in fibroblasts.
AB - 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 αA-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 αA-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 αA-crystallin gene to control high expression in the lens and repression in fibroblasts.
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U2 - 10.1128/mcb.14.11.7363
DO - 10.1128/mcb.14.11.7363
M3 - Article
C2 - 7935450
AN - SCOPUS:0027999510
SN - 0270-7306
VL - 14
SP - 7363
EP - 7376
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 11
ER -