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J. Biol. Chem., Vol. 283, Issue 25, 17030-17038, June 20, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/25/17030    most recent M801637200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gissot, M. Articles by Kim, K. PubMed PubMed Citation Articles by Gissot, M. Articles by Kim, K. Social Bookmarking                      What's this?

High Mobility Group Protein HMGB2 Is a Critical Regulator of Plasmodium Oocyst Development^*

Mathieu Gissot, Li-Min Ting¹, Thomas M. Daly, Lawrence W. Bergman, Photini Sinnis^¶, and Kami Kim¹²

From the Departments of Medicine and of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, the Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, and the ^¶Department of Medical Parasitology, New York University School of Medicine, New York, New York 10010

The sexual cycle of Plasmodium is required for transmission of malaria from mosquitoes to mammals, but how parasites induce the expression of genes required for the sexual stages is not known. We disrupted the Plasmodium yoelii gene encoding high mobility group nuclear factor hmgb2, which encodes a DNA-binding protein potentially implicated in transcriptional regulation of malaria gene expression. We investigated its function in vivo in the vertebrate and invertebrate hosts. pyhmgb2 parasites develop into gametocytes but have drastic impairment of oocyst formation. A global transcriptome analysis of the pyhmgb2 parasites identified 30 genes whose expression is down-regulated in the pyhmgb2 parasites. These genes are conserved in all malaria species, and more than 90% of these genes show a peak of mRNA expression at the gametocyte stage. Surprisingly, the transcripts coding for the Plasmodium berghei orthologues of those genes are stored and translated in the ookinete stage. Therefore, sexual stage protein expression appears to be both transcriptionally and translationally regulated with Plasmodium HMGB2 acting as an important regulator of malaria sexual stage gene expression.

Received for publication, February 28, 2008 , and in revised form, April 8, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant R01 AI056840 (to P. S.). This work was also supported by a Philippe Foundation fellowship (to M. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental data, Figs. 1–3, and Table I.

¹ Supported by Department of Defense Peer Review Medical Research Program Grant W81XWH-05-2-0025.

² To whom correspondence should be addressed: Ullmann 1225, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Tel.: 718-430-2611; E-mail: kkim{at}aecom.yu.edu.

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