falciparum (72). Further analyses also confirmed the colocalization of the heterochromatin protein 1 to H3K9me3, along with their association with regions of the genome that code for Plasmodium virulence factors (73,74). Global histone mass spectrometry analysis also confirmed the prevalence of active acetylated histone marks compared with inhibitory methylated ones (75). All together, these results suggest an atypical euchromatin/heterochromatin structure in the malaria parasite; active chromatin is prevalent

genome-wide, whereas silencing marks are less frequent although they seem to play a significant role in transcriptional control of genes involved in phenotypic variation and pathogenesis. Upon transcriptional activation, eukaryotic promoter Gefitinib nucleosomes are partially removed by sliding or disassembly, allowing DNA to become directly accessible to transcription factors (76,77) and other DNA-binding proteins.

Indeed, various genome-wide analyses provided evidence that active regulatory regions and gene promoters of highly expressed genes are, at least partially, nucleosome-depleted (78,79). Nucleosome positioning is typically driven by active remodelling complexes or dictated by the sequence of the binding DNA itself (80). In particular, poly(dA:dT) tracks are harder to bend around histones, and nucleosomes have a lower affinity for such sequences (81,82). Considering the extremely high AT content of P. falciparum’s YAP-TEAD Inhibitor 1 mouse genome, this latest observation may have important consequences for the parasite’s biology. Recently, the nucleosome landscape of P. falciparum was investigated next in reference to gene regulation by using two genome-wide methods, both coupled to NGS: (i) FAIRE to isolate protein-free DNA; and (ii) micrococcal nuclease-assisted isolation of mononucleosomal elements (MAINE) to isolate DNA fragments associated with histones (13). The combined use of both methods provides a comprehensive view of the chromatin structure across P. falciparum’s genome. Complementary opposite results were obtained by both methods (nucleosome-bound regions were identified with MAINE, and interspacing nucleosome-free

regions were identified with FAIRE) as reflected by a high negative correlation coefficient. Nucleosomes were predominantly found within coding sequences, which have a higher GC content relative to noncoding regions. Similar results were obtained using an anti-histone H4 ChIP-on-chip (52) and are consistent with three recent analyses of nucleosome distribution in human, worms and flies, demonstrating a marked preference of nucleosomes for exons (83–85). Moreover, Ponts et al. demonstrated the occurrence of massive and atypical genome-wide nucleosome depletion at the early trophozoite stage (‘open’ transcriptionally active state) before a progressive repacking of chromatin, while the cycle progresses towards the schizont stage (‘closed’ transcriptionally silent stage) of the intra-erythrocytic cycle.