Functional comparison of the Mus musculus molossinus and Mus musculus domesticus Sry genes

Molecular Endocrinology
R A DubinH Ostrer

Abstract

The Sry gene functions as a genetic switch initiating testicular development of the indifferent mammalian gonad. The Mus musculus molossinus Sry open reading frame (ORF) encodes a 395-amino acid transcription factor (mSry) that specifically binds and bends DNA through its N-terminal HMG domain and activates transcription through its long C-terminal (residues 144-366) glutamine/histidine-rich activation domain. The M. m. domesticus Sry ORF encodes a highly homologous, truncated protein (dSry) of approximately 230 amino acids, and the molecular basis for truncation is a point mutation that creates an amber stop codon within the activation domain. The mSry protein activates transcription of a Sry-responsive reporter gene in HeLa cells, but dSry does not. Gene swapping and in vitro DNA binding experiments revealed that lack of transcriptional activation by dSry was not the result of polymorphisms within the first 137 amino acids of the protein. Direct analysis of the C-terminal glutamine/histidine-rich domain revealed that dSry lacked a functional transcriptional activation domain. Fusion of the GAL4 DNA-binding domain to the C-terminal deletion mutants of the GAL4-mSry chimeric protein indicated that residues 263-345 of the glutam...Continue Reading

Citations

Aug 15, 2006·Molecular and Cellular Endocrinology·Yunmin LiYun-Fai Chris Lau
Jan 18, 2006·Molecular and Cellular Endocrinology·Hyun Ju Oh, Yun-Fai Chris Lau
Jan 24, 2007·Physiological Reviews·Dagmar WilhelmPeter Koopman

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