Fig 6. Enhanced sex-biased expression due to gene repression in the opposite sex.

A. The female-biased gene Slc16a5 is repressed in CAST male liver, resulting in a robust enhancement of female-biased expression in CAST liver (category #6 eQTL). This repression is associated with multiple CAST-specific genetic variants within a strain-shared female-biased peak in the promoter of Slc16a5 that extends into the first intron. CAST is the regulating strain for this gene only in male DO mice (LOD = 12.96 in DO males; regression coefficient, -0.84), while PWK is the regulating strain in female DO mice. The significant female-biased expression seen in CAST liver (48.7-fold F/M) is retained, but at a reduced level in B6 liver (5.5-fold F/M). Browser screenshot shows normalized sequence read signal tracks superimposed by strain. Data presented as in Fig 5. B. Browser screenshot presenting normalized sequence read signal tracks superimposed by sex. This allows direct comparison of normalized sequence read abundance between B6 and CAST mouse liver of the same sex. A reduction of H3K27ac mark accumulation in CAST male liver at the promoter of Slc16a5 enhances the female bias of the CRE (as is characteristic of category #6 eQTL). B6 tracings are shown in blue (male) or pink (female); CAST tracings are shown in green for all tracks.