Developmental switch of CREM function during spermatogenesis: from antagonist to activator

Nature. 1992 Jan 2;355(6355):80-4. doi: 10.1038/355080a0.


Mammalian spermatogenesis consists of a series of complex developmental processes controlled by the pituitary-hypothalamic axis. This flow of biochemical information is directly regulated by the adenylate cyclase signal transduction pathway. We have previously described the CREM (cyclic AMP-responsive element modulator) gene which generates, by cell-specific splicing, alternative antagonists of the cAMP transcriptional response. Here we report the expression of a novel CREM isoform (CREM tau) in adult testis. CREM tau differs from the previously characterized CREM antagonists by the coordinate insertion of two glutamine-rich domains that confer transcriptional activation function. During spermatogenesis there was an abrupt switch in CREM expression. In premeiotic germ cells CREM is expressed at low amounts in the antagonist form. Subsequently, from the pachytene spermatocyte stage onwards, a splicing event generates exclusively the CREM tau activator, which accumulates in extremely high amounts. This splicing-dependent reversal in CREM function represents an important example of developmental modulation in gene expression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Amino Acid Sequence
  • Androgen-Insensitivity Syndrome / genetics
  • Animals
  • Base Sequence
  • Brain / growth & development
  • Brain / physiology*
  • Cyclic AMP Response Element Modulator
  • DNA / genetics
  • DNA / isolation & purification
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Organ Specificity
  • Poly A / genetics
  • Poly A / isolation & purification
  • Polymerase Chain Reaction / methods
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / genetics
  • Repressor Proteins*
  • Sequence Homology, Nucleic Acid
  • Sexual Maturation
  • Spermatogenesis*
  • Testis / growth & development
  • Testis / physiology*


  • DNA-Binding Proteins
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • Repressor Proteins
  • Cyclic AMP Response Element Modulator
  • Poly A
  • RNA
  • DNA