. 2024 Mar 14;187(6):1335-1342.

 doi: 10.1016/j.cell.2024.01.050.

Closing the scissor-shaped curve: Strategies to promote gender equality in academia

Johanna A Joyce ¹, Slavica Masina ², Liliane Michalik ³, Caroline Pot ⁴, Christine Sempoux ⁵, Francesca Amati ⁶

Affiliations expand

• PMID: 38490175
• DOI: 10.1016/j.cell.2024.01.050

Abstract

Gender inequality in STEM fields remains pervasive and undermines the ability for talented individuals to excel. Despite advances, women still encounter obstacles in pursuing academic careers and reaching leadership positions. This commentary discusses the “scissor-shaped curve” and examines effective strategies to fix it, including data-driven initiatives that we have implemented at our university.

Observational Study

. 2024 Feb 28;16(1):36.

 doi: 10.1186/s13148-024-01648-4.

DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study

Céline Dubath ¹, Eleonora Porcu ^2 3 4, Aurélie Delacrétaz ⁵, Claire Grosu ⁵, Nermine Laaboub ⁵, Marianna Piras ⁵, Armin von Gunten ⁶, Philippe Conus ⁷, Kerstin Jessica Plessen ⁸, Zoltán Kutalik ^2 4 9, Chin Bin Eap ^{10 11 12 13}

Affiliations expand

• PMID: 38419113
• PMCID: PMC10903022
• DOI: 10.1186/s13148-024-01648-4

Abstract

Background: Metabolic side effects of psychotropic medications are a major drawback to patients’ successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip.

Results: A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10^-16) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10^-8) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10^-8), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association).

Conclusion: These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role.

Enhancer-promoter interactions become more instructive in the transition from cell-fate specification to tissue differentiation

Tim Pollex ^1 2, Adam Rabinowitz ¹, Maria Cristina Gambetta ^1 3, Raquel Marco-Ferreres ¹, Rebecca R Viales ¹, Aleksander Jankowski ^1 4, Christoph Schaub ¹, Eileen E M Furlong ⁵

. 2024 Mar 11.

Abstract

To regulate expression, enhancers must come in proximity to their target gene. However, the relationship between the timing of enhancer-promoter (E-P) proximity and activity remains unclear, with examples of uncoupled, anticorrelated and correlated interactions. To assess this, we selected 600 characterized enhancers or promoters with tissue-specific activity in Drosophila embryos and performed Capture-C in FACS-purified myogenic or neurogenic cells during specification and tissue differentiation. This enabled direct comparison between E-P proximity and activity transitioning from OFF-to-ON and ON-to-OFF states across developmental conditions. This showed remarkably similar E-P topologies between specified muscle and neuronal cells, which are uncoupled from activity. During tissue differentiation, many new distal interactions emerge where changes in E-P proximity reflect changes in activity. The mode of E-P regulation therefore appears to change as embryogenesis proceeds, from largely permissive topologies during cell-fate specification to more instructive regulation during terminal tissue differentiation, when E-P proximity is coupled to activation.