This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Smith, A. T.
Right arrow Articles by Sullivan, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smith, A. T.
Right arrow Articles by Sullivan, W. J., Jr.

 Previous Article  |  Next Article 

Eukaryotic Cell, December 2005, p. 2057-2065, Vol. 4, No. 12
1535-9778/05/$08.00+0     doi:10.1128/EC.4.12.2057-2065.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

MYST Family Histone Acetyltransferases in the Protozoan Parasite Toxoplasma gondii

Aaron T. Smith,1 Samantha D. Tucker-Samaras,2,{dagger} Alan H. Fairlamb,2 and William J. Sullivan Jr.1*

Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202,1 School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom2

Received 14 July 2005/ Accepted 26 September 2005

The restructuring of chromatin precedes tightly regulated events such as DNA transcription, replication, and repair. One type of chromatin remodeling involves the covalent modification of nucleosomes by histone acetyltransferase (HAT) complexes. The observation that apicidin exerts antiprotozoal activity by targeting a histone deacetyltransferase has prompted our search for more components of the histone modifying machinery in parasitic protozoa. We have previously identified GNAT family HATs in the opportunistic pathogen Toxoplasma gondii and now describe the first MYST (named for members MOZ, Ybf2/Sas3, Sas2, and Tip60) family HATs in apicomplexa (TgMYST-A and -B). The TgMYST-A genomic locus is singular and generates a ~3.5-kb transcript that can encode two proteins of 411 or 471 amino acids. TgMYST-B mRNA is ~7.0 kb and encodes a second MYST homologue. In addition to the canonical MYST HAT catalytic domain, both TgMYST-A and -B possess an atypical C2HC zinc finger and a chromodomain. Recombinant TgMYST-A exhibits a predilection to acetylate histone H4 in vitro at lysines 5, 8, 12, and 16. Antibody generated to TgMYST-A reveals that both the long and short (predominant) versions are present in the nucleus and are also plentiful in the cytoplasm. Moreover, both TgMYST-A forms are far more abundant in rapidly replicating parasites (tachyzoites) than encysted parasites (bradyzoites). A bioinformatics survey of the Toxoplasma genome reveals numerous homologues known to operate in native MYST complexes. The characterization of TgMYST HATs represents another important step toward understanding the regulation of gene expression in pathogenic protozoa and provides evolutionary insight into how these processes operate in eukaryotic cells in general.

* Corresponding author. Mailing address: Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, Medical Sciences Building Room A-525, Indianapolis, IN 46202-5120. Phone: (317) 274-1573. Fax: (317) 274-7714. E-mail: wjsulliv{at}iupui.edu.

{dagger} Present address: Infectious Disease Research, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065.

Eukaryotic Cell, December 2005, p. 2057-2065, Vol. 4, No. 12
1535-9778/05/$08.00+0     doi:10.1128/EC.4.12.2057-2065.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kim, H.-R., Chae, K.-S., Han, K.-H., Han, D.-M. (2009). The nsdC Gene Encoding a Putative C2H2-Type Transcription Factor Is a Key Activator of Sexual Development in Aspergillus nidulans. Genetics 182: 771-783 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»