Characteristic patterns of N Oct-3 binding to a set of neuronal promoters.
N Oct-3, a neurospecific POU protein, homodimerizes in a non-cooperative fashion on the neuronal aromatic l-amino acid decarboxylase gene promoter and generates heterodimers with HNF-3beta. Several other neuronal gene promoters, the corticotropin releasing hormone and the aldolase C gene promoters also contain overlapping binding sites for N Oct-3 and HNF-3beta. We have demonstrated that N Oct-3 presents a non-cooperative homodimerization on these two additional targets and can also give rise to heterodimers with HNF-3beta. Surprisingly, despite the high degree of conservation of the respective POU subunits, the ubiquitous POU protein Oct-1 can only form monomers even in the presence of either N Oct-3 or HNF-3beta on these DNA targets. Our data indicate that this difference is correlated with the specific ability of a portion of the N Oct-3 linker to fold as an alpha-helix, a property shared by class III POU proteins. These results suggest that this novel binding pattern permits the heterodimerization of N Oct-3 and HNF-3beta on the neuronal promoters, which could be a key issue in the development of the nervous system and possibly tumors of neural origin.
Blaud
Magali
M
Laboratoire de Pharmacologie et de Biologie Structurale, CNRS UPR 9062, 205, route de Narbonne, 31077 Toulouse Cedex, France.
Vossen
Christine
C
Joseph
Gérard
G
Alazard
Robert
R
Erard
Monique
M
Nieto
Laurence
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002942:Circular Dichroism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D051542:Hepatocyte Nuclear Factor 3-beta; D051863:Host Cell Factor C1; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D050811:Octamer Transcription Factor-1; D050814:Octamer Transcription Factor-3; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; D050814:Octamer Transcription Factor-3; C494165:POU2F1 protein, human; C494173:POU5F1 protein, human; D021122:Protein Subunits; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta