Identification of candidate regulators of transposable element (TE) expression from host gene/TE coexpression
Authors: Matthew Lawlor; Weihuan Cao; Christopher Ellison
Affiliation: Rutgers University
Keywords: m. computational models; n. other (transposable elements)
The small RNA pathways involved in Drosophila transposable element (TE) control are widely studied, but the role of host transcription factors in regulating TE expression is not well understood. Prior studies show that related TE families show similar expression patterns and tissue specificity. Furthermore, many TEs show expression patterns biased to specific cell types, likely due to regulation by host-encoded trans-acting factors. We reasoned that TE expression should be associated with natural variation in expression of such host-encoded factors across genetic backgrounds in wild populations of Drosophila. To test this hypothesis, we quantified host gene and TE expression in a previously published RNA-seq study of gene expression in 200 Drosophila Genetic Reference Panel strains. We employed linear models to identify significant associations between TE expression and host genes while accounting for confounding factors such as TE copy number and intronic insertions. We additionally correct for a systematic bias affecting highly expressed genes. Our approach identifies 34 previously reported piRNA pathway genes which show negative associations with three or more TEs. We additionally identify 32 transcription factors and cofactors (including seven unnamed genes) showing exclusively positive associations with three or more TEs in both sexes. Another 31 transcription factors and cofactors (including three unnamed genes) are negatively associated with TE expression. For 11 of these 63 candidates, we were able to confirm their effect on TE expression using publicly available RNA-seq after RNAi knockdown in S2R+ cells. We are in the process of performing in-vivo, tissue-specific RNAi knockdowns of additional candidates. These novel TE regulators will shed light on many aspects of host/TE co-evolution including mechanisms by which TEs co-opt host transcription factors to mobilize in the germline as well as both antagonistic and synergistic interactions between host gene regulatory networks and TE expression.