A complex array of positive and negative elements regulates the chicken αA-crystallin gene: Involvement of Pax-6, USF, CREB and/or CREM, and AP-1 proteins

Ales Cvekl, Christina M. Sax, Emery H. Bresnick, Joram Piatigorsky

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7363-7376
Number of pages14
JournalMolecular and Cellular Biology
Volume14
Issue number11
StatePublished - Nov 1994
Externally publishedYes

Fingerprint

Crystallins
Transcription Factor AP-1
Chickens
Lenses
Genes
Proteins
Fibroblasts
Crystalline Lens
DNA-Binding Proteins
Gels
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

A complex array of positive and negative elements regulates the chicken αA-crystallin gene : Involvement of Pax-6, USF, CREB and/or CREM, and AP-1 proteins. / Cvekl, Ales; Sax, Christina M.; Bresnick, Emery H.; Piatigorsky, Joram.

In: Molecular and Cellular Biology, Vol. 14, No. 11, 11.1994, p. 7363-7376.

Research output: Contribution to journalArticle

@article{88392f4626fa4190bc9b22b824f0a27a,
title = "A complex array of positive and negative elements regulates the chicken αA-crystallin gene: Involvement of Pax-6, USF, CREB and/or CREM, and AP-1 proteins",
abstract = "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.",
author = "Ales Cvekl and Sax, {Christina M.} and Bresnick, {Emery H.} and Joram Piatigorsky",
year = "1994",
month = "11",
language = "English (US)",
volume = "14",
pages = "7363--7376",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "11",

}

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, Ales

AU - Sax, Christina M.

AU - Bresnick, Emery H.

AU - Piatigorsky, Joram

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.

UR - http://www.scopus.com/inward/record.url?scp=0027999510&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027999510&partnerID=8YFLogxK

M3 - Article

C2 - 7935450

AN - SCOPUS:0027999510

VL - 14

SP - 7363

EP - 7376

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 11

ER -