Nucleosome landscape and control of transcription in the human malaria parasite
- Nadia Ponts1,6,
- Elena Y. Harris2,6,
- Jacques Prudhomme1,
- Ivan Wick3,
- Colleen Eckhardt-Ludka3,
- Glenn R. Hicks4,
- Gary Hardiman3,5,
- Stefano Lonardi2 and
- Karine G. Le Roch1,7
- 1Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA;
- 2Department of Computer Science and Engineering, University of California, Riverside, California 92521, USA;
- 3BIOGEM, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA;
- 4Center for Plant Cell Biology and Dept of Botany & Plant Sciences, University of California, Riverside, California 92521, USA;
- 5Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA
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↵6 These authors contributed equally to this work.
Abstract
In eukaryotic cells, chromatin reorganizes within promoters of active genes to allow the transcription machinery and various transcription factors to access DNA. In this model, promoter-specific transcription factors bind DNA to initiate the production of mRNA in a tightly regulated manner. In the case of the human malaria parasite, Plasmodium falciparum, specific transcription factors are apparently underrepresented with regards to the size of the genome, and mechanisms underlying transcriptional regulation are controversial. Here, we investigate the modulation of DNA accessibility by chromatin remodeling during the parasite infection cycle. We have generated genome-wide maps of nucleosome occupancy across the parasite erythrocytic cycle using two complementary assays—the formaldehyde-assisted isolation of regulatory elements to extract protein-free DNA (FAIRE) and the MNase-mediated purification of mononucleosomes to extract histone-bound DNA (MAINE), both techniques being coupled to high-throughput sequencing. We show that chromatin architecture undergoes drastic upheavals throughout the parasite's cycle, contrasting with targeted chromatin reorganization usually observed in eukaryotes. Chromatin loosens after the invasion of the red blood cell and then repacks prior to the next cycle. Changes in nucleosome occupancy within promoter regions follow this genome-wide pattern, with a few exceptions such as the var genes involved in virulence and genes expressed at early stages of the cycle. We postulate that chromatin structure and nucleosome turnover control massive transcription during the erythrocytic cycle. Our results demonstrate that the processes driving gene expression in Plasmodium challenge the classical eukaryotic model of transcriptional regulation occurring mostly at the transcription initiation level.
Footnotes
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↵7 Corresponding author.
E-mail karine.leroch{at}ucr.edu; fax (951) 827-3087.
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[Supplemental material is available online at http://www.genome.org. The sequence data from this study have been submitted to the NCBI Short Read Archive (http://www.ncbi.nlm.nih.gov/Traces/sra/sra.cgi) under accession nos. SRA010122 and SRA010123.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.101063.109.
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- Received September 28, 2009.
- Accepted November 30, 2009.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
