title: DNA-encoded nucleosome occupancy is associated with transcription levels in the human malaria parasite Plasmodium falciparum.
abstract: BACKGROUND
  In eukaryotic organisms, packaging of DNA into nucleosomes controls gene expression by regulating access of the promoter to transcription factors. The human malaria parasite Plasmodium falciparum encodes relatively few transcription factors, while extensive nucleosome remodeling occurs during its replicative cycle in red blood cells. These observations point towards an important role of the nucleosome landscape in regulating gene expression. However, the relation between nucleosome positioning and transcriptional activity has thus far not been explored in detail in the parasite.
  
  
  RESULTS
  Here, we analyzed nucleosome positioning in the asexual and sexual stages of the parasite's erythrocytic cycle using chromatin immunoprecipitation of MNase-digested chromatin, followed by next-generation sequencing. We observed a relatively open chromatin structure at the trophozoite and gametocyte stages, consistent with high levels of transcriptional activity in these stages. Nucleosome occupancy of genes and promoter regions were subsequently compared to steady-state mRNA expression levels. Transcript abundance showed a strong inverse correlation with nucleosome occupancy levels in promoter regions. In addition, AT-repeat sequences were strongly unfavorable for nucleosome binding in P. falciparum, and were overrepresented in promoters of highly expressed genes.
  
  
  CONCLUSIONS
  The connection between chromatin structure and gene expression in P. falciparum shares similarities with other eukaryotes. However, the remarkable nucleosome dynamics during the erythrocytic stages and the absence of a large variety of transcription factors may indicate that nucleosome binding and remodeling are critical regulators of transcript levels. Moreover, the strong dependency between chromatin structure and DNA sequence suggests that the P. falciparum genome may have been shaped by nucleosome binding preferences. Nucleosome remodeling mechanisms in this deadly parasite could thus provide potent novel anti-malarial targets.
authors.forename: Evelien M
authors.initials: EM
authors.lastname: Bunnik
authors.forename: Anton
authors.initials: A
authors.lastname: Polishko
authors.forename: Jacques
authors.initials: J
authors.lastname: Prudhomme
authors.forename: Nadia
authors.initials: N
authors.lastname: Ponts
authors.forename: Sarjeet S
authors.initials: SS
authors.lastname: Gill
authors.forename: Stefano
authors.initials: S
authors.lastname: Lonardi
authors.affiliation: Department of Cell Biology and Neuroscience, Center for Disease Vector Research, Institute for Integrative Genome Biology, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA. karine.leroch@ucr.edu.
authors.forename: Karine G
authors.initials: KG
authors.lastname: Le Roch
mesh_terms: D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000469:parasitology* / Q000473:pathology; D008836:Micrococcal Nuclease / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics*; D011067:Poly dA-dT / Q000235:genetics; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D053058:Trophozoites / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D011067:Poly dA-dT; D004247:DNA; D008836:Micrococcal Nuclease