DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis

Abstract

Mutations in the DAX-1 gene are responsible for congenital X-linked adrenal hypoplasia, a disease that is associated with hypogonadotropic hypogonadism. DAX-1 expression is tissue-specific and is finely regulated throughout development, suggesting that it has a role in both adrenal and gonadal function. DAX-1 is an unusual member of the nuclear-receptor superfamily of transcription factors which contains no canonical zinc-finger or any other known DNA-binding motif. Binding sites for DAX-1 are found in the promoters of the dax-1 and StAR (for steroidogenic acute regulatory protein) genes. Here we show that DAX-1 binds DNA and acts as a powerful transcriptional repressor of StAR gene expression, leading to a drastic decrease in steroid production. We provide in vitro and in vivo evidence that DAX-1 binds to DNA hairpin structures. Our results establish DAX-1 as the first member of the nuclear receptor superfamily with novel DNA-binding features and reveal that it has regulatory properties critical to the understanding of its physiological functions.

Sex chromosomes and sex-determining genes: insights from marsupials and monotremes

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A selective view of stochastic inference and modeling problems in nanoscale biophysics

“…A real experimental data set. Let us now consider single-molecule experiments carried by the Xie group at Chemistry Department of Harvard University to study a DNA hairpin molecule, which is a single stranded nucleic acid structure, participating in many important biological processes including the regulation of gene expression [19] , DNA recombination [20] , and the facilitation of mutagenic events [21] . Because of the biological relevance, studying DNA hairpin's conformational properties, such as the conformational fluctuation and energy barrier between the different states, is of current interest.…”