Repressor domain and nuclear localization signal of the murine Hoxa-11 protein are located in the homeodomain: no evidence for role of poly alanine stretches in transcriptional repression.
Hoxa-11 is a member of the homeodomain class of transcription factors, which play important roles in metazoan development. Hoxa-11 is particularly interesting because it is involved in a major mammalian innovation, uterus development and gestation. We are interested in the molecular changes underlying this evolutionary innovation. Although phenotypes resulting from loss of functions are well investigated (e.g., female sterility), little is known about the domains contributing to Hoxa-11 protein function. We therefore mapped the domains mediating two essential transcription factor functions, nuclear localization and transcriptional activity in the mouse Hoxa-11 protein. Our results show that the mammal-specific alanine repeat does not contribute to repressor activity, as has been hypothesized based on amino acid composition and analogy with other repressor domains. Interestingly, both the repressor domain as well as the nuclear localization signal (NLS) are located within the homeodomain, adding to the growing evidence that the homeodomain is a multifunctional domain which fulfills essential transcription factor functions beyond DNA binding. It is proposed that the high degree of conservation of the homeodomain is due to the multiple functional constraints that result from the various conserved functions accommodated in the homeodomain.
Roth
Jutta Johanna
JJ
Department of Ecology and Evolutionary Biology, Yale University, 165 Prospect Street, New Haven, Connecticut 06511, USA.
Breitenbach
Michael
M
Wagner
Günter Paul
GP
D000409:Alanine / Q000032:analysis; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D010957:Plasmids; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C094041:Hoxa11 protein, mouse; D012097:Repressor Proteins; D000409:Alanine