Sry is a transcriptional activator

Robert A. Dubin, Harry Ostrer

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

The SRY gene functions as a genetic switch in gonadal ridge initiating testis determination. The mouse Sry and human SRY open reading frames (ORFs) share a conserved DNA-binding domain (the HMG-box) yet exhibit no additional homology outside this region. As judged by the accumulation of lacZ-SRY hybrid proteins in the nucleus, both the human and mouse SRY ORFs contain a nuclear localization signal. The mouse Sry HMG-box domain selectively binds the sequence NACAAT in vitro when challenged with a random pool of oligonucleotides and binds AACAAT with the highest affinity. When put under the control of a heterologous promotor, the mouse Sry gene activated transcription of a reporter gene containing multiple copies of the AACAAT binding site. Activation was likewise observed for a GAL4-responsive reporter gene, when the mouse Sry gene was linked to the DNA-binding domain of GAL4. Using this system, the activation function was mapped to a glutamine/histidine-rich domain. In addition, LexA-mouse Sry fusion genes activated a LexA-responsive reporter gene in yeast. In contrast, a GAL4- human SRY fusion gene did not cause transcriptional activation. These studies suggest that both the human and the mouse SRY ORFs encode nuclear, DNA- binding proteins and that the mouse Sry ORF can function as a transcriptional activator with separable DNA-binding and activator domains.

Original languageEnglish (US)
Pages (from-to)1182-1192
Number of pages11
JournalMolecular Endocrinology
Volume8
Issue number9
DOIs
StatePublished - Sep 1994
Externally publishedYes

Fingerprint

sry Genes
Open Reading Frames
HMG-Box Domains
Reporter Genes
DNA
Nuclear Localization Signals
Gene Fusion
DNA-Binding Proteins
Glutamine
Histidine
Oligonucleotides
Transcriptional Activation
Testis
Yeasts
Binding Sites
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Sry is a transcriptional activator. / Dubin, Robert A.; Ostrer, Harry.

In: Molecular Endocrinology, Vol. 8, No. 9, 09.1994, p. 1182-1192.

Research output: Contribution to journalArticle

Dubin, Robert A. ; Ostrer, Harry. / Sry is a transcriptional activator. In: Molecular Endocrinology. 1994 ; Vol. 8, No. 9. pp. 1182-1192.
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