title: Plasmodium falciparum heterochromatin protein 1 binds to tri-methylated histone 3 lysine 9 and is linked to mutually exclusive expression of var genes.
abstract: Increasing experimental evidence shows a prominent role of histone modifications in the coordinated control of gene expression in the human malaria parasite Plasmodium falciparum. The search for the histone-mark-reading machinery that translates histone modifications into biological processes, such as formation of heterochromatin and antigenic variation is of foremost importance. In this work, we identified the first member of a histone modification specific recognition protein, an orthologue of heterochromatin protein 1 (PfHP1). Analysis of the PfHP1 amino-acid sequence revealed the presence of the two characteristic HP1 domains: a chromodomain (CD) and a chromo shadow domain (CSD). Recombinant CD binds to di- and tri-methylated lysine 9 from histone H3, but not to unmodified or methylated histone H3 in lysine 4. PfHP1 is able to interact with itself to form dimers, underlying its potential role in aggregating nucleosomes to form heterochromatin. Antibodies raised against PfHP1 detect this molecule in foci at the perinuclear region. ChIP analysis using anti-PfHP1 shows that this protein is linked to heterochromatin of subtelomeric non-coding repeat regions and monoallelic expression of the major virulence var gene family. This is the first report implicating an HP1 protein in the control of antigenic variation of a protozoan parasite.
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (IPN), Apartado Postal 14-740, 07360, México D. F., México.
authors.forename: Karla
authors.initials: K
authors.lastname: Pérez-Toledo
authors.forename: Ana Paola
authors.initials: AP
authors.lastname: Rojas-Meza
authors.forename: Liliana
authors.initials: L
authors.lastname: Mancio-Silva
authors.forename: Nora Adriana
authors.initials: NA
authors.lastname: Hernández-Cuevas
authors.forename: Dulce Maria
authors.initials: DM
authors.lastname: Delgadillo
authors.forename: Miguel
authors.initials: M
authors.lastname: Vargas
authors.forename: Santiago
authors.initials: S
authors.lastname: Martínez-Calvillo
authors.forename: Artur
authors.initials: A
authors.lastname: Scherf
authors.forename: Rosaura
authors.initials: R
authors.lastname: Hernandez-Rivas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry; D037521:Virulence Factors / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D010455:Peptides; D015800:Protozoan Proteins; D037521:Virulence Factors; D000090266:Chromobox Protein Homolog 5; D008239:Lysine