Androgen receptor interactions with Oct-1 and Brn-1 are physically and functionally distinct

Mol Cell Endocrinol. 2002 Apr 25;190(1-2):39-49. doi: 10.1016/s0303-7207(02)00035-7.


POU domain proteins interact positively or negatively with steroid hormone receptors, depending on the precise array of these and other factors assembled on target gene promoters. Octamer transcription factor 1 (Oct-1), a ubiquitous POU factor, is implicated in androgen induction of the mouse sex-limited protein (Slp) gene based on protein-DNA interaction studies. However, direct evidence for a role of Oct-1 in the hormone response has been difficult to obtain. Brain 1 (Brn-1), another POU factor, is more tissue-specific, expressing in brain and also in kidney, which is a major site of Slp synthesis. We compared the interaction of the androgen receptor (AR) with Oct-1 and Brn-1 to reveal the more likely candidate for regulation of Slp. In transfection, addition of either Oct-1 or Brn-1 reduced AR activation, regardless of the presence of an octamer-like sequence in the enhancer, suggesting interference was indirect. However, when the octamer-like element was changed to a consensus octamer site, Brn-1, but not Oct-1, strongly enhanced androgen activation. This correlated with Brn-l's preference for the consensus octamer sequence in DNA binding assays. Direct interaction of AR with glutathione-S-transferase-(GST)-fused Oct-1 was DNA-dependent, while Brn-l-AR association was not. Chimeric Brn-1 and Oct-1 POU domains demonstrated that the DNA-dependent AR interaction relied on the origin of the POU homeodomain. However, in the context of full-length Brn-1 and Oct-1 chimeric proteins, the POU homedomain was not sufficient to confer the distinct behaviors of these factors in vivo, but instead revealed the importance of an N-terminal transactivation domain in Brn-1. These results demonstrate that functional interaction of Oct-1 and Brn-1 with AR is determined by the precise sequence of the octamer binding site, and by differential interaction of the POU factors with AR and other components of the transcriptional machinery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Proteins / genetics
  • Blood Proteins / metabolism*
  • Cell Line
  • Complement C4
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Host Cell Factor C1
  • Mice
  • Nerve Tissue Proteins
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Octamer Transcription Factor-1
  • POU Domain Factors
  • Receptors, Androgen / metabolism*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Blood Proteins
  • C4a protein, mouse
  • Complement C4
  • DNA-Binding Proteins
  • Hcfc1 protein, mouse
  • Homeodomain Proteins
  • Host Cell Factor C1
  • Nerve Tissue Proteins
  • Neuropeptides
  • Octamer Transcription Factor-1
  • POU Domain Factors
  • Pou2f1 protein, mouse
  • Receptors, Androgen
  • Receptors, Glucocorticoid
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • Pou3f3 protein, mouse
  • DNA