Three dimensions of thermolabile sex determination

Abstract

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.high-throughput chromosome conformation capture; TAD, topologically associated domain; Pg, progesterone; PRC, polycomb repressive complex.

How do maternal androgens and estrogens affect sex determination in reptiles with temperature‐dependent sex?

“…A hypothesis proposed by Waters et al (2023) is that chromatin is sensitive to temperature and this would influence the expression of genes related to sexual determination, since it would produce changes in specific transcription regulators. Being thermosensitive, chromatin folding would be affected by temperature, creating changes in the junctions between the enhancer and the promoter, giving rise to a differentiated expression of genes that could bias the gonadal fate to ovaries or testicles.…”