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Science 2 December 1994:
Vol. 266. no. 5190, pp. 1494 - 1500
DOI: 10.1126/science.7985018
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Articles

Science, Vol 266, Issue 5190, 1494-1500
Copyright © 1994 by American Association for the Advancement of Science

articles

Molecular basis of mammalian sexual determination: activation of Mullerian inhibiting substance gene expression by SRY

CM Haqq, CY King, E Ukiyama, S Falsafi, TN Haqq, PK Donahoe, and MA Weiss

Pediatric Surgical Research Laboratory, Massachusetts General Hospital, Boston 02114.

The pathway of male sexual development in mammals is initiated by SRY, a gene on the short arm of the Y chromosome. Its expression in the differentiating gonadal ridge directs testicular morphogenesis, characterized by elaboration of Mullerian inhibiting substance (MIS) and testosterone. SRY and MIS each belong to conserved gene families that function in the control of growth and differentiation. Structural and biochemical studies of the DNA binding domain of SRY (the HMG box) revealed a protein-DNA interaction consisting of partial side chain intercalation into a widened minor groove. Functional studies of SRY in a cell line from embryonic gonadal ridge demonstrated activation of a gene-regulatory pathway leading to expression of MIS. SRY molecules containing mutations associated with human sex reversal have altered structural interactions with DNA and failed to induce transcription of MIS.


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Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Mullerian inhibiting substance promoter.
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Corrections and Clarifications.
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