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

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1994 Nov 1

PMID 7935450

Citations 37

Authors

A Cvekl

C M Sax

E H Bresnick

J Piatigorsky

Affiliations

Soon will be listed here.

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 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.

Citing Articles

Novel clinical presentation and mutation in families with congenital aniridia.

Guo R, Zhang X, Liu A, Ji J, Liu W Front Med (Lausanne). 2022; 9:1042588.

PMID: 36582291 PMC: 9792480. DOI: 10.3389/fmed.2022.1042588.

Systemic and ocular manifestations of a patient with mosaic ARID1A-associated Coffin-Siris syndrome and review of select mosaic conditions with ophthalmic manifestations.

Utz V, Brightman D, Sandoval M, Hufnagel R, Saal H Am J Med Genet C Semin Med Genet. 2020; 184(3):644-655.

PMID: 32888375 PMC: 8808370. DOI: 10.1002/ajmg.c.31839.

Considerations for the use of Cre recombinase for conditional gene deletion in the mouse lens.

Lam P, Padula S, Hoang T, Poth J, Liu L, Liang C Hum Genomics. 2019; 13(1):10.

PMID: 30770771 PMC: 6377743. DOI: 10.1186/s40246-019-0192-8.

The genetic architecture of aniridia and Gillespie syndrome.

Hall H, Williamson K, Fitzpatrick D Hum Genet. 2018; 138(8-9):881-898.

PMID: 30242502 PMC: 6710220. DOI: 10.1007/s00439-018-1934-8.

A comprehensive spatial-temporal transcriptomic analysis of differentiating nascent mouse lens epithelial and fiber cells.

Zhao Y, Zheng D, Cvekl A Exp Eye Res. 2018; 175:56-72.

PMID: 29883638 PMC: 6167154. DOI: 10.1016/j.exer.2018.06.004.

References

Adya N, Zhao L, Huang W, Boros I, Giam C . Expansion of CREB's DNA recognition specificity by Tax results from interaction with Ala-Ala-Arg at positions 282-284 near the conserved DNA-binding domain of CREB. Proc Natl Acad Sci U S A. 1994; 91(12):5642-6. PMC: 44052. DOI: 10.1073/pnas.91.12.5642. View

Kadesch T . Consequences of heteromeric interactions among helix-loop-helix proteins. Cell Growth Differ. 1993; 4(1):49-55. View

Du H, Roy A, Roeder R . Human transcription factor USF stimulates transcription through the initiator elements of the HIV-1 and the Ad-ML promoters. EMBO J. 1993; 12(2):501-11. PMC: 413233. DOI: 10.1002/j.1460-2075.1993.tb05682.x. View

de Jong W, Leunissen J, Voorter C . Evolution of the alpha-crystallin/small heat-shock protein family. Mol Biol Evol. 1993; 10(1):103-26. DOI: 10.1093/oxfordjournals.molbev.a039992. View

Klement J, Cvekl A, Piatigorsky J . Functional elements DE2A, DE2B, and DE1A and the TATA box are required for activity of the chicken alpha A-crystallin gene in transfected lens epithelial cells. J Biol Chem. 1993; 268(9):6777-84. View

Kantorow M, Cvekl A, Sax C, Piatigorsky J . Protein-DNA interactions of the mouse alpha A-crystallin control regions. Differences between expressing and non-expressing cells. J Mol Biol. 1993; 230(2):425-35. DOI: 10.1006/jmbi.1993.1160. View

de Groot R, Sassone-Corsi P . Hormonal control of gene expression: multiplicity and versatility of cyclic adenosine 3',5'-monophosphate-responsive nuclear regulators. Mol Endocrinol. 1993; 7(2):145-53. DOI: 10.1210/mend.7.2.8385737. View

Williams J, Dixon J, Andrisani O . Binding constant determination studies utilizing recombinant delta CREB protein. DNA Cell Biol. 1993; 12(2):183-90. DOI: 10.1089/dna.1993.12.183. View

Meyer T, Habener J . Cyclic adenosine 3',5'-monophosphate response element binding protein (CREB) and related transcription-activating deoxyribonucleic acid-binding proteins. Endocr Rev. 1993; 14(3):269-90. DOI: 10.1210/edrv-14-3-269. View

10.

Bresnick E, Felsenfeld G . Evidence that the transcription factor USF is a component of the human beta-globin locus control region heteromeric protein complex. J Biol Chem. 1993; 268(25):18824-34. View

11.

Czerny T, Schaffner G, Busslinger M . DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site. Genes Dev. 1993; 7(10):2048-61. DOI: 10.1101/gad.7.10.2048. View

12.

Wagner S, Green M . HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization. Science. 1993; 262(5132):395-9. DOI: 10.1126/science.8211160. View

13.

Carriere C, Plaza S, MARTIN P, Quatannens B, Bailly M, Stehelin D . Characterization of quail Pax-6 (Pax-QNR) proteins expressed in the neuroretina. Mol Cell Biol. 1993; 13(12):7257-66. PMC: 364796. DOI: 10.1128/mcb.13.12.7257-7266.1993. View

14.

Zhao L, Adya N, Cross J, Cullen B, Boros I, Giam C . In vitro selection of DNA elements highly responsive to the human T-cell lymphotropic virus type I transcriptional activator, Tax. Mol Cell Biol. 1994; 14(1):456-62. PMC: 358395. DOI: 10.1128/mcb.14.1.456-462.1994. View

15.

Lee D, Gonzalez P, Wistow G . Zeta-crystallin: a lens-specific promoter and the gene recruitment of an enzyme as a crystallin. J Mol Biol. 1994; 236(3):669-78. DOI: 10.1006/jmbi.1994.1178. View

16.

Li H, Yang J, Jacobson R, Pasko D, Sundin O . Pax-6 is first expressed in a region of ectoderm anterior to the early neural plate: implications for stepwise determination of the lens. Dev Biol. 1994; 162(1):181-94. DOI: 10.1006/dbio.1994.1077. View

17.

Sax C, Piatigorsky J . Expression of the alpha-crystallin/small heat-shock protein/molecular chaperone genes in the lens and other tissues. Adv Enzymol Relat Areas Mol Biol. 1994; 69:155-201. DOI: 10.1002/9780470123157.ch5. View

18.

Chepelinsky A, Sommer B, Piatigorsky J . Interaction between two different regulatory elements activates the murine alpha A-crystallin gene promoter in explanted lens epithelia. Mol Cell Biol. 1987; 7(5):1807-14. PMC: 365283. DOI: 10.1128/mcb.7.5.1807-1814.1987. View

19.

Nerenberg M, Hinrichs S, Reynolds R, Khoury G, Jay G . The tat gene of human T-lymphotropic virus type 1 induces mesenchymal tumors in transgenic mice. Science. 1987; 237(4820):1324-9. DOI: 10.1126/science.2888190. View

20.

Hayashi S, Goto K, Okada T, Kondoh H . Lens-specific enhancer in the third intron regulates expression of the chicken delta 1-crystallin gene. Genes Dev. 1987; 1(8):818-28. DOI: 10.1101/gad.1.8.818. View