Background The functional determinants of H3K4me3, their potential dependency on histone H2B monoubiquitination, and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike in Saccharomyces cerevisiae , where a single SET1 protein catalyzes H3K4me3 as part of COMPlex of proteins ASsociated with Set1 (COMPASS), in Arabidopsis thaliana , this activity involves multiple histone methyltransferases. Among these, the plant-specific SET DOMAIN GROUP 2 (SDG2) has a prominent role. Results We report that SDG2 co-regulates hundreds of genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of yeast COMPASS. We show that S2Lb co-purifies with the AtCOMPASS core subunit WDR5, and both S2Lb and SDG2 directly influence H3K4me3 enrichment over highly transcribed genes. S2Lb knockout triggers pleiotropic developmental phenotypes at the vegetative and reproductive stages, including reduced fertility and seed dormancy. However, s2lb seedlings display little transcriptomic defects as compared to the large repertoire of genes targeted by S2Lb, SDG2, or H3K4me3, suggesting that H3K4me3 enrichment is important for optimal gene induction during cellular transitions rather than for determining on/off transcriptional status. Moreover, unlike in budding yeast, most of the S2Lb and H3K4me3 genomic distribution does not rely on a trans -histone crosstalk with histone H2B monoubiquitination. Conclusions Collectively, this study unveils that the evolutionarily conserved COMPASS-like complex has been co-opted by the plant-specific SDG2 histone methyltransferase and mediates H3K4me3 deposition through an H2B monoubiquitination-independent pathway in Arabidopsis. Electronic supplementary material The online version of this article (10.1186/s13059-019-1705-4) contains supplementary material, which is available to authorized users.
IMPORTANCE Factors contributing to underrepresentation of women in surgery are incompletely understood. Pro-male bias and stereotype threat appear to contribute to gender imbalance in surgery.OBJECTIVES To evaluate the association between pro-male gender bias and career engagement and the effect of stereotype threat on skill performance among trainees in academic surgery. DESIGN, SETTING, AND PARTICIPANTSA 2-phase study with a double-blind, randomized clinical trial component was conducted in 3 academic general surgery training programs. Residents were recruited between August 1 and August 15, 2018, and the study was completed at the end of that academic year. In phase 1, surveys administered 5 to 6 months apart investigated the association of gender bias with career engagement. In phase 2, residents were randomized 1:1 using permuted-block design stratified by site, training level, and gender to receive either a trigger of or protection against stereotype threat. Immediately after the interventions, residents completed the Fundamentals of Laparoscopic Surgery (FLS) assessment followed by a final survey. A total of 131 general surgery residents were recruited; of these 96 individuals with academic career interests met eligibility criteria; 86 residents completed phase 1. Eighty-five residents were randomized in phase 2, and 4 residents in each arm were lost to follow-up.INTERVENTION Residents read abstracts that either reported that women had worse laparoscopic skill performance than men (trigger of stereotype threat [A]) or had no difference in performance (protection against stereotype threat [B]). MAIN OUTCOMES AND MEASURESAssociation between perception of pro-male gender bias and career engagement survey scores (phase 1) and stereotype threat intervention and FLS scores (phase 2) were the outcomes. Intention-to-treat analysis was conducted.RESULTS Seventy-seven residents (38 women [49.4%]) completed both phases of the study. The association between pro-male gender bias and career engagement differed by gender (interaction coefficient, −1.19; 95% CI, −1.90 to −0.49; P = .02); higher perception of bias was associated with higher engagement among men (coefficient, 1.02; 95% CI, 0.19-2.24; P = .04), but no significant association was observed among women (coefficient, −0.25; 95% CI, −1.59 to 1.08; P = .50). There was no evidence of a difference in FLS score between interventions (mean [SD], A: 395 [150] vs B: 367 [157]; P = .51). The response to stereotype threat activation was similar in men and women (interaction coefficient, 15.1; 95% CI, −124.5 to 154.7; P = .39). The association between stereotype threat activation and FLS score differed by gender across levels of susceptibility to stereotype threat (interaction coefficient, −35.3; 95% CI, −47.0 to −23.6; P = .006). Higher susceptibility to stereotype threat was associated with lower FLS scores among women who received a stereotype threat trigger (coefficient, −43.4; 95% CI, −48.0 to −38.9; P = .001).CONCLUSIONS AND RELEVANCE Perception of pro-male bias and ...
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