The histone demethylase KDM6B regulates temperature-dependent sex determination in a turtle species

Abstract

Temperature-dependent sex determination is a notable model of phenotypic plasticity. In many reptiles, including the red-eared slider turtle (), the individual's sex is determined by the ambient temperature during egg incubation. In this study, we show that the histone H3 lysine 27 (H3K27) demethylase KDM6B exhibits temperature-dependent sexually dimorphic expression in early embryos before the gonad is distinct. Knockdown of at 26°C (a temperature at which all offspring develop into males) triggers male-to-female sex reversal in >80% of surviving embryos. KDM6B directly promotes the transcription of the male sex-determining gene by eliminating the trimethylation of H3K27 near its promoter. Additionally, overexpression of is sufficient to rescue the sex reversal induced by disruption of This study establishes causality and a direct genetic link between epigenetic mechanisms and temperature-dependent sex determination in a turtle species.

Climate change, sex reversal and lability of sex‐determining systems

“…The importance of evolution in a wild population will depend on the standing variation in temperature sensitivity and the generation of new variation relative to the rate of climatic change. New variation may arise faster than mutation rates if there is plasticity in temperature sensitivity due to nongenetic mechanisms (e.g., Deveson et al, 2017;Ge et al, 2018;Piferrer, 2013;Schwanz, Janzen, & Proulx, 2010).…”

Thermal Response of Epigenetic Genes Informs Turtle Sex Determination with and without Sex Chromosomes

“…Differential transcription has been documented for many TSD and GSD turtle homologs of the genes in the regulatory network of mammalian gonadal development [Lovell-Badge et al, 2002;Eggers et al, 2014], and some evidence exists that epigenetic modifications such as DNA and histone methylation mediate some of the observed differential tran-scription in TSD taxa [Matsumoto et al, 2013;Radhakrishnan et al, 2017a;Ge et al, 2018]. A recent study demonstrated that differential transcription of epigenetic genes can be a powerful tool to identify candidate epigenetic processes involved in sexual development in TSD turtles that help guide subsequent functional assays [Ge et al, 2018]. Because regulation of gene expression can involve other epigenetic processes beyond methylation, including various forms of histone tail modifications and RNA interference [Jaenisch and Bird, 2003], here we explored for the first time the extent to which the transcription of this epigenetic machinery is also thermosensitive.…”

“…Following the lead from such differential transcription evidence, it was recently demonstrated that the higher gene expression of Kdm6b at male-producing temperatures (MPT) in slider turtles yields higher KDM6D protein levels which act to remove the triple methylation of the histone H3K27 bound at the promoter of Dmrt1 , thus activating this testis development gene as part of the male differentiation cascade [Ge et al, 2018]. Despite these significant advances, whether TSD is mediated by just a couple types of epigenetic modifications or by many remains unknown.…”

Insights into Emydid Turtle Cytogenetics: The European Pond Turtle as a Model Species

“…However, Glyptemys is an exception, because all the other species of the group apparently have TSD. Ge et al [2018] propose that TSD in turtles might be epigenetic based on findings in the chromatin modifier gene Kdm6b . However, it cannot be excluded that TSD-classified species have cryptic sex chromosomes with an underlying GSD mechanism [Ezaz et al .…”