Epigenomic modifications predict active promoters and gene structure in Toxoplasma gondii

被引:92
作者
Gissot, Mathieu
Kelly, Krystyna A.
Ajioka, James W.
Greally, John M.
Kim, Kami [1 ]
机构
[1] Albert Einstein Coll Med, Dept Med Infect Dis, Bronx, NY 10467 USA
[2] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA
[3] Univ Cambridge, Dept Pathol, Cambridge CB2 1TN, England
[4] Inst Publ Hlth, Med Res Council Biostat Unit, Cambridge, England
[5] Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA
基金
英国医学研究理事会; 英国惠康基金;
关键词
D O I
10.1371/journal.ppat.0030077
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Mechanisms of gene regulation are poorly understood in Apicomplexa, a phylum that encompasses deadly human pathogens like Plasmodium and Toxoplasma. Initial studies suggest that epigenetic phenomena, including histone modifications and chromatin remodeling, have a profound effect upon gene expression and expression of virulence traits. Using the model organism Toxoplasma gondii, we characterized the epigenetic organization and transcription patterns of a contiguous 1% of the T. gondii genome using custom oligonucleotide microarrays. We show that methylation and acetylation of histones H3 and H4 are landmarks of active promoters in T. gondii that allow us to deduce the position and directionality of gene promoters with > 95% accuracy. These histone methylation and acetylation "activation'' marks are strongly associated with gene expression. We also demonstrate that the pattern of histone H3 arginine methylation distinguishes certain promoters, illustrating the complexity of the histone modification machinery in Toxoplasma. By integrating epigenetic data, gene prediction analysis, and gene expression data from the tachyzoite stage, we illustrate feasibility of creating an epigenomic map of T. gondii tachyzoite gene expression. Further, we illustrate the utility of the epigenomic map to empirically and biologically annotate the genome and show that this approach enables identification of previously unknown genes. Thus, our epigenomics approach provides novel insights into regulation of gene expression in the Apicomplexa. In addition, with its compact genome, genetic tractability, and discrete life cycle stages, T. gondii provides an important new model to study the evolutionarily conserved components of the histone code.
引用
收藏
页码:709 / 719
页数:11
相关论文
共 39 条
[21]   A high-resolution map of active promoters in the human genome [J].
Kim, TH ;
Barrera, LO ;
Zheng, M ;
Qu, CX ;
Singer, MA ;
Richmond, TA ;
Wu, YN ;
Green, RD ;
Ren, B .
NATURE, 2005, 436 (7052) :876-880
[22]   Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome [J].
Liang, GN ;
Lin, JCY ;
Wei, VV ;
Yoo, C ;
Cheng, JC ;
Nguyen, CT ;
Weisenberger, DJ ;
Egger, G ;
Takai, D ;
Gonzales, FA ;
Jones, PA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (19) :7357-7362
[23]   TOXOPLASMIC ENCEPHALITIS IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME [J].
LUFT, BJ ;
HAFNER, R ;
KORZUN, AH ;
LEPORT, C ;
ANTONISKIS, D ;
BOSLER, EM ;
BOURLAND, DD ;
UTTAMCHANDANI, R ;
FUHRER, J ;
JACOBSON, J ;
MORLAT, P ;
VILDE, JL ;
REMINGTON, JS .
NEW ENGLAND JOURNAL OF MEDICINE, 1993, 329 (14) :995-1000
[24]   Identification and characterisation of a regulatory region in the Toxoplasma gondii hsp70 genomic locus [J].
Ma, YF ;
Zhang, YW ;
Kim, K ;
Weiss, LM .
INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2004, 34 (03) :333-346
[25]  
Martin S, 2001, Neonatal Netw, V20, P23
[26]   The transcription machinery and the molecular toolbox to control gene expression in Toxoplasma gondii and other protozoan parasites [J].
Meissner, M ;
Soldati, D .
MICROBES AND INFECTION, 2005, 7 (13) :1376-1384
[27]  
Oberley MJ, 2004, METHOD ENZYMOL, V376, P315
[28]   Genome-wide map of nucleosorne acetylation and methylation in yeast [J].
Pokholok, DK ;
Harbison, CT ;
Levine, S ;
Cole, M ;
Hannett, NM ;
Lee, TI ;
Bell, GW ;
Walker, K ;
Rolfe, PA ;
Herbolsheimer, E ;
Zeitlinger, J ;
Lewitter, F ;
Gifford, DK ;
Young, RA .
CELL, 2005, 122 (04) :517-527
[29]   The transcriptome of Toxoplasma gondii [J].
Radke, JR ;
Behnke, MS ;
Mackey, AJ ;
Radke, JB ;
Roos, DS ;
White, MW .
BMC BIOLOGY, 2005, 3 (1)
[30]   The genomic landscape of histone modifications in human T cells [J].
Roh, Tae-Young ;
Cuddapah, Suresh ;
Cui, Kairong ;
Zhao, Keji .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (43) :15782-15787