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

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

PROVIDER: PRJNA640953 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12064732_1.fastq.gz	Fastqsanger.gz
	SRR12064732_2.fastq.gz	Fastqsanger.gz
	SRR12064733_1.fastq.gz	Fastqsanger.gz
	SRR12064733_2.fastq.gz	Fastqsanger.gz
	SRR12064734_1.fastq.gz	Fastqsanger.gz

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

Project description:Anopheles gambiae mosquitoes are primary human malaria vectors, but we know very little about their mechanisms of transcriptional regulation. We profiled chromatin accessibility by ATAC-seq in laboratory-reared An. gambiae mosquitoes experimentally infected with the human malaria parasite Plasmodium falciparum. By integrating ATAC-seq, RNA-seq and ChIP-seq data we showed a positive correlation between accessibility at promoters and introns, gene expression and active histone marks. By comparing expression and chromatin structure patterns in different tissues, we were able to infer cis-regulatory elements controlling tissue specific gene expression and to predict the in vivo binding sites of relevant transcription factors. The ATAC-seq assay also allowed the precise mapping of active regulatory regions, including novel transcription start sites and enhancers that annotate to mosquito immune-response genes. This study is important not only for advancing our understanding of mechanisms of transcriptional regulation in the mosquito vector of human malaria, but also the information we produced is of great potential for developing new mosquito-control and anti-malaria strategies.

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

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

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Anopheles gambiae immune responses to human and rodent Plasmodium parasite species

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Project description:Alternative splicing (AS) is a highly conserved mechanism that allows to expand the coding capacity of the genome, by modifying how multiple isoforms are expressed or used to generate different phenotypes. Despite its importance in physiology and disease, genome-wide studies of AS are lacking in most insects, including mosquitoes. Even for model organisms, chromatin associated processes involved in the regulation AS are poorly known. In this study, we investigated AS in the mosquito Anopheles gambiae in the context of tissue-specific gene expression and mosquito responses to a Plasmodium falciparum infection, as well as the relationship between patterns of differential isoform expression and usage with chromatin accessibility changes. For this, we combined RNA-seq and ATAC-seq data from A. gambiae midguts and salivary glands, and from infected and non-infected midguts. We report differences between tissues in the expression of 456 isoforms and in the use of 211 isoforms. Secondly, we find a clear and significant association between chromatin accessibility states and tissue-specific patterns of AS. The analysis of differential accessible regions located at splicing sites permitted the identification of several motifs resembling the binding sites of Drosophila transcription factors. Finally, the genome-wide analysis of tissue-dependent enhancer activity revealed that approximately 20% of A. gambiae transcriptional enhancers annotate to a differentially expressed or used isoform and that their activation status is linked to AS differences between tissues. This research illuminates the role of AS in gene expression in vector mosquitoes, and identifies regulatory regions potentially involved in AS regulation, which could reveal novel strategies for vector control.

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Alternative splicing and its regulation in the malaria vector Anopheles gambiae

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