The regulatory genome of the malaria vector Anopheles gambiae: integrating chromatin accessibility and gene expression

Background Anopheles gambiae mosquitoes are the primary vectors for the transmission of human malaria in Africa. Despite their importance from a global health perspective, we know very little about the regulatory elements controlling functional gene expression.

Results We performed genome-wide profiling of chromatin accessibility by ATAC-seq in midguts and salivary glands of laboratory-reared An. gambiae mosquitoes experimentally infected with Plasmodium falciparum. Our results show that accessibility localized preferentially in promoters and in introns. The integration of ATAC-seq data with the transcriptome revealed by RNA-seq, and with ChIP-seq data, showed accessibility correlated positively both with gene expression, and with histone marks associated with active chromatin (H3K9ac/H3K27ac). The differential analysis of chromatin accessibility and the expression profiles of target genes between tissues allowed us to infer cis-regulatory elements controlling tissue specific gene expression, including functions linked to mosquito genes related to immune responses, like def1 or gam1. Additionally, the analysis of enriched motifs allowed us to predict the in vivo binding sites of tissue-specific transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including TSS- and enhancer-like elements that annotate to genes with roles in malaria infection such as lrim1.

Conclusion This study identifies genome-wide regulatory regions likely to play an essential function in the regulation of gene expression in An. gambiae. This study is important not only for advancing our understanding of the regulatory genome of the mosquito vector of human malaria, but also for possible application to the genetic manipulation of mosquitoes.