High mobility group protein HMGB2 is a critical regulator of Plasmodium oocyst development

Mathieu Gissot, Li Min Ting, Thomas M. Daly, Lawrence W. Bergman, Photini Sinnis, Kami Kim

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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. Δpyhmgb2 parasites develop into gametocytes but have drastic impairment of oocyst formation. A global transcriptome analysis of the Δpyhmgb2 parasites identified ∼30 genes whose expression is down-regulated in the Δpyhmgb2 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.

Original languageEnglish (US)
Pages (from-to)17030-17038
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number25
DOIs
StatePublished - Jun 20 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Gissot, M., Ting, L. M., Daly, T. M., Bergman, L. W., Sinnis, P., & Kim, K. (2008). High mobility group protein HMGB2 is a critical regulator of Plasmodium oocyst development. Journal of Biological Chemistry, 283(25), 17030-17038. https://doi.org/10.1074/jbc.M801637200