Skip to main content
. 2017 Jun 14;3(6):e1700731. doi: 10.1126/sciadv.1700731

Fig. 4. Model for role of JARID2/JMJD3 differential IR in temperature-dependent sex.

Fig. 4

(A) Phylogenetic relationships of reptile lineages, coded for genetic sex determination (GSD; blue) and/or TSD (red), and occurrence of sex-associated JARID2/JMJD3 IR (asterisk). (B to D) The sex-determining action of JARID2/JMJD3 IR is to divert sexual differentiation from the ancestral homogametic state (the default path) to the alternate developmental pathway. (B) At moderate temperatures, JARID2/JMJD3 mRNA is spliced, exported, and translated. JARID2 facilitates recruitment of PRC2 to target genes, which are repressed via H3K27 trimethylation (26–28). JARID2 and/or JMJD3 may also directly activate genes via histone demethylation (14). (C) At extreme temperatures, introns are retained in JARID2/JMJD3 mRNA. IR may be induced by binding of CIRBP (6, 37) to JARID2/JMJD3 transcripts. IR isoforms are not exported or translated (24, 25). JARID2 is depleted from PRC2, reducing recruitment to target genes. Direct activation of genes by JARID2/JMJD3-catalyzed histone demethylation is also perturbed. The epigenetic landscape is thereby altered, repressing genes that maintain the default sex pathway and/or activating sex reversal genes. This can lead to feminization or masculinization, depending on the ancestral GSD system in a given species (8, 31, 32). (D) Four possible sex-associated patterns of IR may occur. Left: Ancestral GSD states (ZZ/ZW or XX/XY), with sex reversal at either high (beige) or low (blue) temperatures. Mating of sex-reversed and wild-type homogametic individuals causes transition to TSD (9, 30), with JARID2/JMJD3 IR maintained as the regulatory signal controlling differentiation. Right: Four TSD patterns emerge: female-specific IR at high temperatures, male-specific IR at low temperatures, female-specific IR at low temperatures, and male-specific IR at high temperatures.