Abstract

BackgroundInfection by the human malaria parasite leads to important changes in mosquito 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 blood-fed uninfected and infected with natural isolates of the human malaria parasite Plasmodium falciparum in Burkina Faso.ResultsWe report 15,916 regions containing differential histone modification enrichment between infected and uninfected, of which 8339 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, antimicrobial peptides-encoding genes, and genes related to melanization responses and the complement system. Further, the motif analysis of regions differentially enriched in various histone modifications predicts binding sites that might be involved in the cis-regulation of these 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.ConclusionsThe analysis of malaria infection-induced chromatin changes in mosquitoes is important not only to identify regulatory elements and genes underlying mosquito responses to P. falciparum infection, but also for possible applications to the genetic manipulation of mosquitoes and to other mosquito-borne systems.

Highlights

  • Infection by the human malaria parasite leads to important changes in mosquito phenotypic traits related to vector competence

  • We aim to provide a comprehensive understanding of the chromatin and the transcriptional responses induced by P. falciparum infection of A. gambiae in the conditions found in a malaria endemic area in Africa

  • We found similar numbers of peaks in the infected and uninfected mosquitoes and a high correlation in the ChIP-seq profiles (Additional file 4: Figure S1A), indicating that histone modification profiles are comparable between the two conditions

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Summary

Introduction

Infection by the human malaria parasite leads to important changes in mosquito phenotypic traits related to vector competence. These modifications can remain during cell division, leaving a record of gene activity, i.e., epigenetic memory, that affects or primes the transcriptional response later in life [12, 18,19,20,21,22,23,24] In mosquitoes, despite their relevance to human health, there is very little knowledge of chromatin regulation and its link to mosquito immunity, physiology and behavior [25]. Recent reports revealed the role of various transcription factors, such as REL2, lola and Deaf, 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 what are the molecular players involved in these malariainduced responses

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