The HNF-3 gene family of transcription factors in mice: gene structure, cDNA sequence, and mRNA distribution.

The rat HNF-3 (hepatocyte nuclear factor 3) gene family encodes three transcription factors known to be important in the regulation of gene expression in liver and lung. We have cloned and characterized the mouse genes and cDNAs for HNF-3 alpha, beta, and gamma and analyzed their expression patterns in various adult tissues and mouse embryonic stages. The HNF-3 proteins are highly conserved between mouse and rat, with the exception of the amino terminus of HNF-3 gamma, which in mouse is more similar to those of HNF-3 alpha and beta than to the amino termini of the rat HNF-3 gamma protein. The mouse HNF-3 genes are small and contain only two or three (HNF-3 beta) exons with conserved intron-exon boundaries. The proximal promoter of the mouse HNF-3 beta gene is remarkably similar to that of the previously cloned rat HNF-3 beta gene, but is different from the promoters of the HNF-3 alpha and gamma genes. The mRNA distribution of the mouse HNF-3 genes was analyzed by quantitative RNase protection with gene-specific probes. While HNF-3 alpha and beta are restricted mainly to endoderm-derived tissues (lung, liver, stomach, and small intestine), HNF-3 gamma is more extensively expressed, being present additionally in ovary, testis, heart, and adipose tissue, but missing from lung. Transcripts for HNF-3 beta and alpha are detected most abundantly in midgestation embryos (Day 9.5), while HNF-3 gamma expression peaks around Day 15.5 of gestation.

[1]  W. Knöchel,et al.  Activin A induced expression of a fork head related gene in posterior chordamesoderm (notochord) of Xenopus laevis embryos , 1992, Mechanisms of Development.

[2]  R. Gaynor,et al.  Characterization and chromosomal mapping of the gene encoding the cellular DNA binding protein ILF. , 1992, Genomics.

[3]  K. Zaret,et al.  An active tissue-specific enhancer and bound transcription factors existing in a precisely positioned nucleosomal array , 1993, Cell.

[4]  E. Lai,et al.  Hepatocyte nuclear factor 3 beta contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila fork head protein , 1992, Molecular and cellular biology.

[5]  R. Costa,et al.  The restricted promoter activity of the liver transcription factor hepatocyte nuclear factor 3 beta involves a cell-specific factor and positive autoactivation , 1992, Molecular and cellular biology.

[6]  A. R. I. Altaba.  Pintallavis , a gene expressed in the organizer and midline cells of frog embryos: involvement in the development of the neural axis , 1999 .

[7]  J. Darnell,et al.  Differential regulation of hepatocyte-enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells. , 1991, The New biologist.

[8]  J. Darnell,et al.  Transcriptional control in hepatocytes: a window on development. , 1991, Trends in biochemical sciences.

[9]  B. Stripp,et al.  The lung-specific CC10 gene is regulated by transcription factors from the AP-1, octamer, and hepatocyte nuclear factor 3 families , 1993, Molecular and cellular biology.

[10]  H. Jäckle,et al.  Developmentally regulated Drosophila gene family encoding the fork head domain. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[11]  B. Dujon,et al.  The complete DNA sequence of yeast chromosome III , 1992, Nature.

[12]  M. Zakin,et al.  Liver‐enriched HNF‐3α and ubiquitous factors interact with the human transferrin gene enhancer , 1993 .

[13]  K. Kaestner,et al.  Differentiation-induced gene expression in 3T3-L1 preadipocytes. A second differentially expressed gene encoding stearoyl-CoA desaturase. , 1989, The Journal of biological chemistry.

[14]  J E Darnell,et al.  Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes , 1989, Molecular and cellular biology.

[15]  E. Lai,et al.  Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing rat brain , 1992, Neuron.

[16]  R. Cortese,et al.  Transcriptional regulation of liver-specific gene expression , 1991, Current Biology.

[17]  R. Cortese,et al.  The transcriptional regulation of liver-specific gene expression. , 1991, Oxford surveys on eukaryotic genes.

[18]  R. Gaynor,et al.  Characterization and chromosomal mapping of the gene encoding the cellular DNA binding protein HTLF. , 1992, Genomics.

[19]  M. Jamrich,et al.  A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain. , 1992, Genes & development.

[20]  A. Riggs,et al.  Genomic sequencing. , 1993, Methods in molecular biology.

[21]  E. Lai,et al.  Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[22]  G. Crabtree,et al.  A transcriptional hierarchy involved in mammalian cell-type specification , 1992, Nature.

[23]  G. Schütz,et al.  Activation of the tyrosine aminotransferase gene is dependent on synergy between liver-specific and hormone-responsive elements. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[24]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[25]  H. Jäckle,et al.  The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo , 1989, Cell.

[26]  R. Gaynor,et al.  Cloning of a cellular factor, interleukin binding factor, that binds to NFAT-like motifs in the human immunodeficiency virus long terminal repeat. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[27]  B. Hogan,et al.  Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. , 1993, Development.

[28]  S. Henikoff.  Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. , 1984, Gene.

[29]  D Weigel,et al.  The fork head domain: A novel DNA binding motif of eukaryotic transcription factors? , 1990, Cell.

[30]  R. Chalkley,et al.  Interaction of a liver-specific factor with an enhancer 4.8 kilobases upstream of the phosphoenolpyruvate carboxykinase gene , 1990, Molecular and cellular biology.

[31]  F. Bosch,et al.  Two genetically defined trans-acting loci coordinately regulate overlapping sets of liver-specific genes , 1990, Cell.

[32]  G. Church,et al.  Genomic sequencing. , 1993, Methods in molecular biology.

[33]  P. Vogt,et al.  The retroviral oncogene qin belongs to the transcription factor family that includes the homeotic gene fork head. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[34]  M. Monk,et al.  HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells , 1987, Nature.

[35]  K. Kaestner,et al.  Six members of the mouse forkhead gene family are developmentally regulated. , 1993, Proceedings of the National Academy of Sciences of the United States of America.