In schizonts H3K9Me1 is more peripheral but there are areas of partial colocalization with Nup100 towards the cytoplasm. In the ring stage, these two proteins co-localize almost completely which indicates that part of Nup100 is also targeted to the PV. Taken together, these data ML-265 suggest that nuclear periphery is potentially the main area of chromatin-dependent regulation of gene expression. However, it also shows that a significant portion of Plasmodium nuclear proteins is targeted away from the nuclei; in particular to the PV. In this work, we characterized the intracellular distribution of 5 histone modifications that have not previously been investigated in P. falciparum. All four histone acetylations exhibited a strong concentration around the nuclear periphery in a horseshoe-like pattern that has been previously demonstrated with H3K4Me3. With the exception of H4K8Ac, this pattern was conserved in all developmental stages of the IDC. In other eukaryotic species, these four acetylations are typically associated with epigenetic regulation of gene expression associated either with actively transcribed genes in Venlafaxine euchromatin or silenced genes in heterochromatin. The peripheral nuclear distribution of these histone modifications in P. falciparum is consistent with the emerging model of the spatial organization of epigenetic gene regulation in eukaryotic cells. According to this model, genes that are under strong epigenetic activation and/or suppression localize to distinct regions distributed along the nuclear periphery. In Saccharomyces cerevisiae, many silenced genes are targeted to discrete domains along the nuclear envelope, while active genes are located in distinct chromatin domains that are anchored to the components of the nuclear pores. Lopez-Rubio et al demonstrated the existence of at least one type of a gene silencing compartment at the periphery of the P. falciparum nuclei. This discrete compartment is delineated by H3K9Me3 and is involved in silencing of the var gene family that is located at the chromosomal subtelomeres and encodes important factors for host-parasite interaction.
All four histone acetylations exhibited a strong concentration
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