Figure 1.

Biological function of Sry and structure of the HMG box. (A) Scheme of the initiation of male-sex differentiation in therian mammals. SRY (red) plays a key role in this process by activating expression of SOX9, which then autoactivates itself, leading to stage-specific expression of FGF9 and PGDS as indicated by green arrows. (B) Ribbon representation of the HMG box of the human SRY HMG box-DNA complex (PDB coordinates 1J46), HMG domain in light gray ribbon and DNA shown as atomic spheres with carbon (C) tan, nitrogen (N) blue, oxygen (O) red, and phosphorus (P) orange). Residues for which clinically relevant variants have been identified are shown in black stick models (Y72 in red). The major wing is formed by the confluence of the three helices in the L-shaped domain (3). The minor wing is formed upon DNA binding (gold circle). (C) Expanded view of the minor wing and the DNA-dependent hydrophobic mini-core (4). Residues of the hydrophobic mini-core are shown as stick models (methyl groups of the N-terminal Val 5 are shown as spheres); Y72F is shown in red. (D) Chromosomal locations of S9 upstream enhancer elements for rat, human, and mouse chromosomes. TESCO [testis enhancer sequence core (5)] is in gray, further upstream is Enhancer 13 (Enh13 (6),) region in blue. (E) Identification of consensus transcription factor binding elements within the 535 bp of the human Enh13 region. Binding site elements were identified using PROMO (7, 8).