Using Transcriptomes as Mutant Phenotypes Reveals Functional Regions of a Mediator Subunit in Caenorhabditis elegans
Although transcriptomes have recently been used as phenotypes with which to perform epistasis analyses, they are not yet used to study intragenic function/structure relationships. We developed a theoretical framework to study allelic series using transcriptomic phenotypes. As a proof-of-concept, we apply our methods to an allelic series of dpy-22, a highly pleiotropic Caenorhabditis elegans gene orthologous to the human gene MED12, which encodes a subunit of the Mediator complex. Our methods identify functional units within dpy-22 that modulate Mediator activity upon various genetic programs, including the Wnt and Ras modules.
© 2018 Genetics Society of America. Received May 12, 2018. Revision received June 29, 2018. Accepted July 5, 2018. This article would not be possible without help from Igor Antoshechkin and Vijaya Kumar who performed the library preparation and sequencing. Han Wang, Hillel Schwartz, Erich Schwarz, and Carmie Puckett Robinson provided valuable input throughout the project. This work was supported by National Institutes of Health (NIH) grant U41 HG002223, by the Millard and Muriel Jacobs Genetics and Genomics Laboratory at California Institute of Technology, and by the Howard Hughes Medical Institute, with which Paul W. Sternberg was an investigator.
Submitted - 210724.full.pdf
Supplemental Material - SI1_dpy_22_results.csv