DNA-encoded nucleosome occupancy is associated with transcription levels in the human malaria parasite Plasmodium falciparum

BMC Genomics

Karine G Le Roch²  Stefano Lonardi¹  Sarjeet S Gill²  Nadia Ponts³  Jacques Prudhomme²  Anton Polishko¹  Evelien M Bunnik² 

[1]Department of Computer Science and Engineering, University of California, Riverside, Riverside, CA 92521, USA

[2]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

[3]Present Address: Mycology and Food Safety, INRA Centre de Bordeaux-Aquitaine, Villenave d’Ornon Cedex 33883, France

关键词: Sequence;    Transcription;    Nucleosome;    Cell cycle;    Malaria;   

Others  :  1217251
DOI  :  10.1186/1471-2164-15-347

 received in 2014-01-09, accepted in 2014-04-30,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Bunnik et al.; licensee BioMed Central Ltd.

【 图 表 】

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