DNA Binding Activity of Recombinant SRY from Normal Males and XY Females

TLDR

The human SRY gene encodes a testis‑determining protein containing a high‑mobility group (HMG) box similar to that of the T cell‑specific DNA‑binding protein TCF‑1. Recombinant SRY binds the AACAAAG core sequence in a sequence‑dependent manner, but point mutations in the HMG box of XY females abolish or markedly reduce this binding, demonstrating that DNA‑binding activity is essential for sex determination.

Abstract

The protein encoded by the human testis determining gene, SRY, contains a high mobility group (HMG) box related to that present in the T cell-specific, DNA-binding protein TCF-1. Recombinant SRY protein was able to bind to the same core sequence AACAAAG recognized by TCF-1 in a sequence dependent manner. In five XY females point mutations were found in the region encoding the HMG box. In four cases DNA binding activity of mutant SRY protein was negligible; in the fifth case DNA binding was reduced. These results imply that the DNA binding activity of SRY is required for sex determination.