Malaria parasites undergo a complex life cycle in the human host and the mosquito vector. The ApiAP2 family of DNA-binding proteins plays a dominant role in parasite development and life cycle progression. Most ApiAP2 factors studied to date act as transcription factors regulating stage-specific gene expression. Here, we characterized an ApiAP2 factor in Plasmodium falciparum that we termed PfAP2-HC. We demonstrate that PfAP2-HC specifically binds to heterochromatin throughout the genome. Intriguingly, PfAP2-HC does not bind DNA in vivo and recruitment of PfAP2-HC to heterochromatin is independent of its DNA-binding domain but strictly dependent on heterochromatin protein 1. Furthermore, our results suggest that PfAP2-HC functions neither in the regulation of gene expression nor in heterochromatin formation or maintenance. In summary, our findings reveal PfAP2-HC as a core component of heterochromatin in malaria parasites and identify unexpected properties and substantial functional divergence among the members of the ApiAP2 family of regulatory proteins.

The prefrontal cortex (PFC) is one of the latest brain regions to mature, which allows the acquisition of complex cognitive abilities through experience. To unravel the underlying gene expression changes during postnatal development, we performed RNA-sequencing (RNA-seq) in the rat medial PFC (mPFC) at five developmental time points from infancy to adulthood, and analyzed the differential expression of protein-coding genes, long intergenic noncoding RNAs (lincRNAs), and alternative exons. We showed that most expression changes occur in infancy, and that the number of differentially expressed genes reduces toward adulthood. We observed 137 differentially expressed lincRNAs and 796 genes showing alternative exon usage during postnatal development. Importantly, we detected a genetic switch from neuronal network establishment in infancy to maintenance of neural networks in adulthood based on gene expression dynamics, involving changes in protein-coding and lincRNA gene expression as well as alternative exon usage. Our gene expression datasets provide insights into the multifaceted transcriptional regulation of the developing PFC. They can be used to study the basic developmental processes of the mPFC and to understand the mechanisms of neurodevelopmental and neuropsychiatric disorders. Our study provides an important contribution to the ongoing efforts to complete the "brain map", and to the understanding of PFC development.

Malaria parasites undergo a highly complex life cycle in the human host and the mosquito vector. The ApiAP2 family of sequence-specific DNA-binding proteins plays a dominant role in parasite development and life cycle progression. Of the ApiAP2 factors studied to date, most act as transcription factors regulating stage-specific gene expression. Here, we characterised a new ApiAP2 factor in Plasmodium falciparum (PF3D7_1456000) that we termed PfAP2-HC. Via detailed investigation of several single or double genetically engineered parasite lines, we demonstrate that PfAP2-HC specifically binds to heterochromatin throughout the genome. Intriguingly, PfAP2-HC does not bind DNA in vivo and recruitment of PfAP2-HC to heterochromatin is independent of its DNA-binding domain but strictly dependent on heterochromatin protein 1. Furthermore, our results suggest that PfAP2-HC functions neither in the regulation of gene expression nor in heterochromatin formation or maintenance. In summary, our findings reveal that PfAP2-HC constitutes a core component of heterochromatin in malaria parasites. They furthermore identify unexpected properties of ApiAP2 factors and suggest substantial functional divergence among the members of this important family of regulatory proteins.

Malaria parasites undergo a complex life cycle in the human host and the mosquito vector. The ApiAP2 family of DNA-binding proteins plays a dominant role in parasite development and life cycle progression. Most ApiAP2 factors studied to date act as transcription factors regulating stage-specific gene expression. Here, we characterized an ApiAP2 factor in Plasmodium falciparum that we termed PfAP2-HC. We demonstrate that PfAP2-HC specifically binds to heterochromatin throughout the genome. Intriguingly, PfAP2-HC does not bind DNA in vivo and recruitment of PfAP2-HC to heterochromatin is independent of its DNA-binding domain but strictly dependent on heterochromatin protein 1. Furthermore, our results suggest that PfAP2-HC functions neither in the regulation of gene expression nor in heterochromatin formation or maintenance. In summary, our findings reveal PfAP2-HC as a core component of heterochromatin in malaria parasites and identify unexpected properties and substantial functional divergence among the members of the ApiAP2 family of regulatory proteins.