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e-Article

The chromatin bound proteome of the human malaria parasite
Document Type
article
Source
Microbial Genomics. 6(2)
Subject
Biochemistry and Cell Biology
Bioinformatics and Computational Biology
Genetics
Biological Sciences
Vector-Borne Diseases
Human Genome
Malaria
Rare Diseases
Infectious Diseases
Biotechnology
1.1 Normal biological development and functioning
Aetiology
Underpinning research
2.2 Factors relating to the physical environment
Generic health relevance
Infection
Good Health and Well Being
Chromatin
Gene Expression Regulation
Genome
Protozoan
Humans
Malaria
Falciparum
Plasmodium falciparum
Protein Binding
Proteome
Protozoan Proteins
chromatin structure
proteome
chromatin-associated proteins
topological data analysis
Microbiology
Language
Abstract
Proteins interacting with DNA are fundamental for mediating processes such as gene expression, DNA replication and maintenance of genome integrity. Accumulating evidence suggests that the chromatin of apicomplexan parasites, such as Plasmodium falciparum, is highly organized, and this structure provides an epigenetic mechanism for transcriptional regulation. To investigate how parasite chromatin structure is being regulated, we undertook comparative genomics analysis using 12 distinct eukaryotic genomes. We identified conserved and parasite-specific chromatin-associated domains (CADs) and proteins (CAPs). We then used the chromatin enrichment for proteomics (ChEP) approach to experimentally capture CAPs in P. falciparum. A topological scoring analysis of the proteomics dataset revealed stage-specific enrichments of CADs and CAPs. Finally, we characterized, two candidate CAPs: a conserved homologue of the structural maintenance of chromosome 3 protein and a homologue of the crowded-like nuclei protein, a plant-like protein functionally analogous to animal nuclear lamina proteins. Collectively, our results provide a comprehensive overview of CAPs in apicomplexans, and contribute to our understanding of the complex molecular components regulating chromatin structure and genome architecture in these deadly parasites.