Fig 9. Fine-tuning of Sry expression is achieved by the balance in activities between H3K9 demethylase Jmjd1a and H3K9 methyltransferase GLP/G9a complex.

In wild-type embryonic gonads, Jmjd1a removes H3K9 methylation marks, which were deposited by GLP/G9a complex, from the Sry locus, thereby ensuring Sry activation. In Jmjd1a-deficient embryonic gonads, the absence of Jmjd1a results in the GLP/G9a complex-mediated H3K9 hypermethylation at the Sry locus, thereby compromising Sry expression and causing male-to-female sex reversal. Normalization of the H3K9 methylation balance of the Sry locus by a genetic or a pharmacological approach rescues the aberrant sex development of Jmjd1a-deficient mice by restoring Sry expression.