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Nucleic Acids Research, 2000, Vol. 28, No. 4 1026-1035
© 2000 Oxford University Press

Fusions with histone H3 result in highly specific alteration of gene expression

Nhuan Ha1, Karen Hellauer1 and Bernard Turcotte1,2,3,*

1Department of Medicine, Royal Victoria Hospital and 2Department of Biochemistry and 3Department of Microbiology and Immunology, McGill University, 687 Pine Avenue West, Montréal, Québec H3A 1A1, Canada

Hap1 is a yeast transcriptional activator which controls expression of genes such as CYC1 and CYC7. Our results show that Hap1 activity is dependent on a functional chromatin remodeling complex SWI/SNF. Using a modified two-hybrid screen with Hap1 as bait, we recovered expression vectors encoding the Gal4 activation domain fused to histone H3 [Gal4(AD)–H3]. Hap1 activity at CYC1 or CYC7 was increased by Gal4(AD)–H3 and the effect was dependent on the presence of the activation domain of Hap1 and a functional SWI complex. Importantly, overexpression of H3 alone had no effect on Hap1 activity. Analysis of Gal4(AD)–H3 revealed that the fusion is not incorporated into the nucleosome while a functional Gal4 activation domain is dispensable. Activity of many other transcriptional activators was unchanged or slightly affected in the presence of Gal4(AD)–H3. Thus, our results identify a new class of histone H3 variants that cause highly specific alteration of gene expression. Hap1 may interact directly with H3 favoring chromatin remodeling by the SWI/SNF complex.

* To whom correspondence should be addressed at: Department of Medicine, Room H7.82, Royal Victoria Hospital, 687 Pine Avenue West, Montréal, Québec H3A 1A1, Canada. Tel: +1 514 842 1231 ext. 5046; Fax: +1 514 982 0893; Email: turcotte@lan1.molonc.mcgill.ca


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