Three dimensions of thermolabile sex determination

The molecular mechanism of temperature-dependent sex determination (TSD) is a long-standing mystery. How is the thermal signal sensed, captured and transduced to regulate key sex genes? Although there is compelling evidence for pathways via which cells capture the temperature signal, there is no known mechanism by which cells transduce those thermal signals to affect gene expression. Here we propose a novel hypothesis we call 3D-TSD (the three dimensions of thermolabile sex determination). We postulate that the genome has capacity to remodel in response to temperature by changing 3D chromatin conformation, perhaps via temperature-sensitive transcriptional condensates. This could rewire enhancer-promoter interactions to alter the expression of key sex-determining genes. This hypothesis can accommodate monogenic or multigenic thermolabile sex-determining systems, and could be combined with upstream thermal sensing and transduction to the epigenome to commit gonadal fate.

Automated summary

The molecular mechanism of temperature-dependent sex determination (TSD) is still unknown, particularly how cells transduce thermal signals to affect gene expression. A new hypothesis called 3D-TSD suggests that the genome can remodel in response to temperature by changing 3D chromatin conformation, potentially rewiring enhancer-promoter interactions to alter key sex-determining genes. This hypothesis can explain both monogenic and multigenic thermolabile sex-determining systems and can be integrated with thermal sensing and transduction to the epigenome.