Chromatin changes in Anopheles gambiae induced by a Plasmodium falciparum infection

Abstract

Infection by the human malaria parasite leads to important changes in phenotypic traits related to vector competence. However, we still lack a clear understanding of the underlying mechanisms and in particular, of the epigenetic basis for these changes. We have examined genome-wide distribution maps of H3K27ac, H3K9ac, H3K9me3 and H3K4me3 by ChIP-seq and the transcriptome by RNA-seq, of midguts from Anopheles gambiae mosquitoes infected by the human malaria parasite Plasmodium falciparum. We report 15,916 regions containing differential histone modification enrichment, of which 8,339 locate at promoters and/or intersect with genes. The functional annotation of these regions allowed us to identify infection responsive genes showing differential enrichment in various histone modifications such as CLIP proteases, anti-microbial peptides encoding genes and genes related to melanization responses and the complement system. Further, the motif analysis of differential histone enriched regions predicts binding sites that might be involved in the cis-regulation of this regions such as Deaf1, Pangolin and Dorsal transcription factors (TFs). Some of these TFs are known to regulate immunity gene expression in Drosophila and are involved in the Notch and JAK/STAT signaling pathways. The analysis of malaria infection-induced chromatin changes in mosquitoes is important not only to identify regulatory elements and genes underlying mosquito responses to a malaria infection but also for possible applications to the genetic manipulation of mosquitoes and extension to other mosquito-borne systems.fications of histones (hPTMs) impact the structure and/or function of chromatin, with different histone marks yielding distinct functional consequences [13]. For example, in Drosophila, as in other organisms, H3K27ac, H3K9ac and H3K4me3 are linked to gene activation and localize at promoters, whereas H3K9me3 is associated with silencing and occupies broader regions [14]. Various combinations of active and repressive histone modifications define chromatin states that are linked to gene function [15][16][17]. These modifications can remain, leaving a record of gene activity, i.e. epigenetic memory, that affect or prime the transcriptional response later in life [12,[18][19][20][21][22][23][24]. In mosquitoes, despite their relevance for human health, there is very little knowledge on chromatin regulation and its link to mosquito immunity, physiology and behavior [25]. In a previous study, we characterized genome-wide occupancy patterns of various histone modifications and established a link between hPTMs and gene expression profiles in midguts and salivary glands of the human malaria vector A. gambiae [26]. In addition, recent reports reveal the role of various transcription factors such as REL2, lola and Deaf1, in A. gambiae immune defenses [27, 28]. These findings have set the stage for additional studies aimed at understanding how the chromatin landscape is altered in P. falciparum infected mosquito tissues and which are the molecular pla...

Anopheles gambiaematernal age and parous state control offspring susceptibility toPlasmodium falciparum

“…Both age and nutritional conditions of mothers have been implicated in epigenetic driven maternal effect in vertebrates (34,36) and in invertebrates (37)(38)(39). Whereas epigenetic inheritance studies are expanding in Drosophila and Caenorhabditis elegans, little is known in Anopheles mosquitoes, notably at the molecular level (4,21,25,28,40,41). Epigenetic investigation is therefore likely one leading area to develop in understanding the phenotypic results reported in this manuscript.…”