The sex-determining region of the human Y chromosome encodes a finger protein

Cell. 1987 Dec 24;51(6):1091-104. doi: 10.1016/0092-8674(87)90595-2.


The presence or absence of the Y chromosome determines whether a mammalian embryo develops as a male or female. In humans, genetic deletion analysis of "sex-reversed" individuals has identified a small portion of the Y chromosome necessary and sufficient to induce testicular differentiation of the bipotential gonad. We report the cloning of a 230-kilobase segment of the human Y chromosome that contains some or all of the testis-determining factor gene (TDF), the master sex-determining locus. The cloned region spans the deletion in a female who carries all but 160 kilobases of the Y. Certain DNA sequences within this region were highly conserved during evolution; homologs occur on the Y chromosomes of all mammals examined. In particular, homologous sequences are found within the sex-determining region of the mouse Y chromosome. The nucleotide sequence of this conserved DNA on the human Y chromosome suggests that it encodes a protein with multiple "finger" domains, as first described in frog transcription factor IIIA. The encoded protein probably binds to nucleic acids in a sequence-specific manner, and may regulate transcription. Very similar DNA sequences occur on the X chromosome of humans and other mammals. We discuss the possibility that the Y-encoded finger protein is the testis-determining factor, and propose models of sex determination accommodating the finding of a related locus on the X chromosome. The presence of similar sequences in birds suggests a possible role not only in the XX/XY sex determination system of mammals, but also in the ZZ/ZW system of birds.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Evolution
  • Cloning, Molecular
  • DNA-Binding Proteins*
  • Female
  • Genes
  • Gonadal Steroid Hormones / genetics*
  • Humans
  • Kruppel-Like Transcription Factors
  • Male
  • Mammals
  • Molecular Sequence Data
  • Sequence Homology, Nucleic Acid
  • Sex Determination Analysis*
  • Sex Differentiation
  • Transcription Factors
  • Transcription, Genetic
  • X Chromosome
  • Y Chromosome*


  • DNA-Binding Proteins
  • Gonadal Steroid Hormones
  • Kruppel-Like Transcription Factors
  • Transcription Factors
  • ZFY protein, human

Associated data

  • GENBANK/J03134