Fig. 1.

A) Overview of mammalian sex determination. In mice, gonads form at E10.5 and are indistinguishable between XY and XX individuals. The somatic progenitor cells that compose the fetal gonad (top) are initially bipotential. Following expression of the Y-encoded Sry gene at E11.5, progenitor cells differentiate into Sertoli cells and gonads develop as testes (left). In absence of Sry, progenitor cells differentiate into pregranulosa cells and gonads develop as ovaries (right). Commitment to the male or female fate requires repression of the alternate pathway. B) The chromatin landscape at the bipotential stage. Male- and female-determining genes are bivalent and co-expressed at low and similar levels in progenitor cells (top, yellow). Upregulation of male-determining genes leading to differentiation of Sertoli cells (left, blue) is accompanied by loss of the repressive H3K27me3 mark, whereas repressed female-determining genes remain bivalent. Upregulation of female-determining genes leading to differentiation of pregranulosa cells (right, pink) is accompanied by loss of the repressive H3K27me3 mark, whereas repressed male-determining genes remain bivalent.