Investigation of a CBP-Driven Mechanism of Anopheles Mosquito Dosage Compensation

INTRODUCTION: Dosage compensation is the essential mechanism by which X-linked gene expression is regulated between the sexes. Recent studies on Anopheles mosquitoes suggest that SOA/007, a homolog of the Drosophila Tramtrack protein, drives this process. However, further questions about the role of SOA/007 in mosquito dosage compensation remain unanswered. Another protein may be more central to this mechanism.

METHODS: We employed a multi-pronged approach to uncover evidence for a role of another protein in Anopheles dosage compensation. Protein database searches, homology comparisons, literature searches, and analyses of existing histone modification datasets were used to infer a potential role for CBP in this process.

RESULTS: Drosophila Tramtrack blocks inappropriate assembly of the dosage compensation complex at non-dosage compensated sites on Drosophila male X chromosomes. There is no evidence of enhanced H4K16ac at dosage-compensated mosquito genes. Working with the NuRD complex, Tramtrack may recruit CBP-dependent H3.3 incorporation and H3K56ac-driven activation from polycomb repression while exiting development on the mosquito male X chromosome. We provide a literature- and histone modification data-based argument in support of this conclusion.

CONCLUSIONS/DISCUSSION: Further studies are needed to better understand the mechanisms of dosage compensation in mosquitoes. Enhanced application of molecular biology techniques will be the key to gathering the necessary data. Dosage compensation provides further opportunities to identify targets useful for mosquito-borne disease prevention strategies.