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Molecular and Cellular Biology, August 2006, p. 5969-5982, Vol. 26, No. 16
0270-7306/06/$08.00+0     doi:10.1128/MCB.00696-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Differential Gene Regulation by Selective Association of Transcriptional Coactivators and bZIP DNA-Binding Domains{dagger}

Benoit Miotto and Kevin Struhl*

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115

Received 22 April 2006/ Returned for modification 12 May 2006/ Accepted 2 June 2006

bZIP DNA-binding domains are targets for viral and cellular proteins that function as transcriptional coactivators. Here, we show that MBF1 and the related Chameau and HBO1 histone acetylases interact with distinct subgroups of bZIP proteins, whereas pX does not discriminate. Selectivity of Chameau and MBF1 for bZIP proteins is mediated by residues in the basic region that lie on the opposite surface from residues that contact DNA. Chameau functions as a specific coactivator for the AP-1 class of bZIP proteins via two arginine residues. A conserved glutamic acid/glutamine in the linker region underlies MBF1 specificity for a subgroup of bZIP factors. Chameau and MBF1 cannot synergistically coactivate transcription due to competitive interactions with the basic region, but either protein can synergistically coactivate with pX. Analysis of Jun derivatives that selectively interact with these coactivators reveals that MBF1 is crucial for the response to oxidative stress, whereas Chameau is important for the response to chemical and osmotic stress. Thus, the bZIP domain mediates selective interactions with coactivators and hence differential regulation of gene expression.


* Corresponding author. Mailing address: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115. Phone: (617) 432-2104. Fax: (617) 432-2529. E-mail: kevin{at}hms.harvard.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.


Molecular and Cellular Biology, August 2006, p. 5969-5982, Vol. 26, No. 16
0270-7306/06/$08.00+0     doi:10.1128/MCB.00696-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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