title: High-mobility-group box nuclear factors of Plasmodium falciparum.
abstract: In eukaryotes, the high-mobility-group (HMG) nuclear factors are highly conserved throughout evolution and are divided into three families, including HGMB, characterized by an HMG box domain. Some HMGB factors are DNA structure specific and preferentially interact with distorted DNA sequences, trigger DNA bending, and hence facilitate the binding of nucleoprotein complexes that in turn activate or repress transcription. In Plasmodium falciparum, two HMGB factors were predicted: PfHMGB1 and PfHMGB2. They are small proteins, under 100 amino acids long, encompassing a characteristic HMG box domain closely related to box B of metazoan factors, which comprises two HMG box domains, A and B, in tandem. Computational analyses supported the conclusion that the Plasmodium proteins were genuine architectural HMGB factors, and in vitro analyses performed with both recombinant proteins established that they were able to interact with distorted DNA structures and bend linear DNA with different affinities. These proteins were detected in both asexual- and gametocyte-stage cells in Western blotting experiments and mainly in the parasite nuclei. PfHMGB1 is preferentially expressed in asexual erythrocytic stages and PfHMGB2 in gametocytes, in good correlation with transcript levels of expression. Finally, immunofluorescence studies revealed differential subcellular localizations: both factors were observed in the nucleus of asexual- and sexual-stage cells, and PfHMGB2 was also detected in the cytoplasm of gametocytes. In conclusion, in light of differences in their levels of expression, subcellular localizations, and capacities for binding and bending DNA, these factors are likely to play nonredundant roles in transcriptional regulation of Plasmodium development in erythrocytes.
authors.affiliation: INSERM, U511, Université Pierre et Marie Curie, Paris VI, Centre Hospitalo-Universitaire de la Pitié-Salpêtrière, 91 boulevard de l'Hôpital, 75013 Paris, France. briquet@ext.jussieu.fr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Briquet
authors.forename: Charlotte
authors.initials: C
authors.lastname: Boschet
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gissot
authors.forename: Emilie
authors.initials: E
authors.lastname: Tissandié
authors.forename: Elisa
authors.initials: E
authors.lastname: Sevilla
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Franetich
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thiery
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Hamid
authors.forename: Catherine
authors.initials: C
authors.lastname: Bourgouin
authors.forename: Catherine
authors.initials: C
authors.lastname: Vaquero
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D004247:DNA / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D024002:HMGB Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008018:Life Cycle Stages; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D016415:Sequence Alignment
chemical_list: D024002:HMGB Proteins; D004247:DNA