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Molecular and Cellular Biology, September 2009, p. 4604-4611, Vol. 29, No. 17
0270-7306/09/$08.00+0     doi:10.1128/MCB.00160-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Noncanonical Bromodomain in the AAA ATPase Protein Yta7 Directs Chromosomal Positioning and Barrier Chromatin Activity{triangledown}

Angeline Gradolatto,1 Sherri K. Smart,1,{dagger} Stephanie Byrum,1,{dagger} Lauren P. Blair,1,{dagger},{ddagger} Richard S. Rogers,2 Elizabeth A. Kolar,3 Heather Lavender,1 Signe K. Larson,1 John D. Aitchison,2 Sean D. Taverna,3 and Alan J. Tackett1*

University of Arkansas for Medical Sciences, Department of Biochemistry and Molecular Biology, Little Rock, Arkansas 72205,1 Institute for Systems Biology, Seattle, Washington 98103,2 Johns Hopkins School of Medicine, Baltimore, Maryland 212053

Received 4 February 2009/ Returned for modification 7 March 2009/ Accepted 21 June 2009

Saccharomyces cerevisiae Yta7 is a barrier active protein that modulates transcriptional states at the silent mating locus, HMR. Additionally, Yta7 regulates histone gene transcription and has overlapping functions with known histone chaperones. This study focused on deciphering the functional role of the noncanonical Yta7 bromodomain. By use of genetic and epistasis analyses, the Yta7 bromodomain was shown to be necessary for barrier activity at HMR and to have overlapping functions with histone regulators (Asf1 and Spt16). Canonical bromodomains can bind to acetylated lysines on histones; however, the Yta7 bromodomain showed an association with histones that was independent of posttranslational modification. Further investigation showed that regions of Yta7 other than the bromodomain conferred histone association. Chromatin immunoprecipitation-chip analyses revealed that the Yta7 bromodomain was not solely responsible for histone association but was also necessary for proper chromosomal positioning of Yta7. This work demonstrates that the Yta7 bromodomain engages histones for certain cellular functions like barrier chromatin maintenance and particular Spt16/Asf1 cellular pathways of chromatin regulation.


* Corresponding author. Mailing address: University of Arkansas for Medical Sciences, Department of Biochemistry and Molecular Biology, 4301 West Markham Street, Little Rock, AR 72205. Phone: (501) 686-8152. Fax: (501) 686-8169. E-mail: ajtackett{at}uams.edu

{triangledown} Published ahead of print on 6 July 2009.

{dagger} These authors contributed equally.

{ddagger} Present address: Yale University School of Medicine, Department of Pathology, New Haven, CT 06520.


Molecular and Cellular Biology, September 2009, p. 4604-4611, Vol. 29, No. 17
0270-7306/09/$08.00+0     doi:10.1128/MCB.00160-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.