Chromatin structure and functional analysis of the mouse HNF3alpha gene.
The transcription factor HNF3alpha is a member of the winged-helix family of regulatory proteins. It is expressed in the definitive endoderm, notochord, and neural tube in embryos, but in the adult is expressed primarily in endoderm-derived tissues such as liver, lung, and pancreas. We present here the cloning of the mouse HNF3alpha gene and a characterization of its chromatin structure and regulatory sequences. The HNF3alpha gene is encoded by two exons and its transcription initiates at multiple start sites at a TATA-less promoter that is highly conserved between mouse and rat. We found different patterns of DNaseI hypersensitive sites in HNF3alpha gene chromatin in different adult tissues in which HNF3alpha is expressed, suggesting distinct regulatory mechanisms occurring within different tissue derivatives of the endoderm germ layer. Cell transfection data indicate that sequences spanning certain upstream hypersensitive sites can enhance transcription from the HNF3alpha promoter, but only when stably integrated into chromatin and not when transiently transfected. The results suggest a complex regulatory interplay between distinct genetic regulatory sequences that function specifically in chromatin.
Lodmell
A G
AG
Department of Molecular Biology, Cell Biology, Biochemistry, Brown University, Box G-J363, Providence, RI 02912, USA.
Jung
J
J
Zaret
K S
KS
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002843:Chromatin / Q000235:genetics*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D005809:Genes, Regulator; D051541:Hepatocyte Nuclear Factor 3-alpha; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D002843:Chromatin; D004268:DNA-Binding Proteins; C496500:Foxa1 protein, mouse; C496501:Foxa1 protein, rat; D051541:Hepatocyte Nuclear Factor 3-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA