A distal dimerization domain is essential for DNA-binding by the atypical HNF1 homeodomain.
Hepatic Nuclear Factor 1 (HNF1, also referred to as LFB1, HP1 or APF) is a liver-specific transcription factor required for the expression of many hepatocyte specific genes. We report here the purification of this rat liver nuclear protein and the cloning of its cDNA using a PCR-derived approach. Seven independent clones reveal 3 alternative polyadenylation sites and a unique open reading frame. Both a motif homologous to the homeodomain and a distal dimerization domain are required for specific DNA binding. Sequence comparisons reveal several atypical features at key positions in the segment corresponding to helices III and IV of the Antaennapedia homeodomain as well as a potential 24 amino acid loop in place of the universal turn between helices II and III. Together with its property to dimerize in the presence or absence of DNA, these features place HNF1 as the prototype of a novel subclass of transcription factors distantly related to homeoproteins.
Chouard
T
T
UA 1149, CNRS, Département de Biologie Moléculaire, Institut Pasteur, Paris, France.
Blumenfeld
M
M
Bach
I
I
Vandekerckhove
J
J
Cereghini
S
S
Yaniv
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D016366:Open Reading Frames; D011061:Poly A; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D011061:Poly A