Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
Abstract

HNF-1 alpha (previously referred to as HNF-1, LPB1, and APF) is a vertebrate transcription factor that contains a divergent homeo domain and plays a prominent role in regulating genes that have the common characteristic of being expressed in hepatocytes and a complex group of endodermally and mesodermally derived tissues. HNF-1 alpha is unique among the vertebrate homeo domain-containing proteins in that it dimerizes in the absence of its DNA recognition sequence, suggesting the possibility that the function of HNF-1 alpha may be diversified by forming heterodimers with other related proteins. We report the initial characterization of HNF-1 beta, which is closely related to HNF-1 alpha and is able to form heterodimers with HNF-1 alpha in vitro. Although HNF-1 alpha, but not HNF-1 beta, is expressed in the liver, HNF-1 alpha and HNF-1 beta are coexpressed in the murine Hepa1A cell line and in the mammalian kidney where a subset of hepatocyte genes are expressed. In contrast, exclusive expression of HNF-1 beta is associated with repression of a subset of hepatocyte-specific genes in the dedifferentiated hepatocyte cell line C2, differentiated F9 cells, in somatic hybrids between hepatocytes and fibroblasts, and in the lung. The extent of heterodimerization may be regulated in a tissue-specific way because freely exchangeable heterodimers are formed in Jurkat T cells transfected with HNF-1 alpha and HNF-1 beta, whereas in liver cells stable homodimers are present. These studies define a pair of homeo domain proteins that have the potential to interact to produce an embryologically complex pattern of gene expression.

Bibliography

Mendel, D. B., Hansen, L. P., Graves, M. K., Conley, P. B., & Crabtree, G. R. (1991). HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes & Development, 5(6), 1042–1056.

Authors 5
  1. D B Mendel (first)
  2. L P Hansen (additional)
  3. M K Graves (additional)
  4. P B Conley (additional)
  5. G R Crabtree (additional)
References 64 Referenced 234
  1. 10.1016/0092-8674(90)90147-7
  2. 10.1002/j.1460-2075.1988.tb03095.x / EMBO J. / A variant nuclear protein in dedifferentiated hepatoma cells binds to the same functional sequences in the β fibrinogen gene promoter as HNF-1. (1988)
  3. 10.1101/gad.4.3.372
  4. 10.1016/S0021-9258(19)50881-X / J. Biol. Chem. / A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. (1952)
  5. 10.1016/0092-8674(90)90214-Y
  6. 10.1016/0003-2697(76)90527-3
  7. 10.1101/gad.2.8.957
  8. 10.1016/0092-8674(88)90076-1
  9. 10.1093/nar/18.19.5853
  10. {'key': '2021111320181458000_5.6.1042.10', 'first-page': '2633', 'article-title': 'Liver-specific RNA metabolism in hepatoma cells: Variations in transcription rates in mRNA levels.', 'volume': '5', 'year': '1985', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Liver-specific RNA metabolism in hepatoma cells: Variations in transcription rates in mRNA levels. (1985)
  11. 10.1126/science.3499668
  12. 10.1073/pnas.85.21.7937
  13. Darnell, J.E., H. Lodish, and D. Baltimore. 1986. Molecular cell biology. Scientific American Books, New York.
  14. {'key': '2021111320181458000_5.6.1042.14', 'first-page': '1603', 'article-title': 'Characterization of differentiated and dedifferentiated clones of a rat hepatoma.', 'volume': '56', 'year': '1974', 'journal-title': 'Biochimie'} / Biochimie / Characterization of differentiated and dedifferentiated clones of a rat hepatoma. (1974)
  15. 10.1016/0092-8674(80)90095-1
  16. 10.1101/gad.4.9.1541
  17. 10.1016/0092-8674(90)90095-V
  18. 10.1016/0092-8674(90)90708-M
  19. 10.1016/0092-8674(89)90877-5
  20. 10.1093/nar/9.23.6505
  21. 10.1002/j.1460-2075.1987.tb02424.x / EMBO J. / Hepatoma variants (C2) are defective for transcriptional and post-transcriptional actions from both endogenous and viral genomes. (1987)
  22. 10.1073/pnas.85.17.6347
  23. {'key': '2021111320181458000_5.6.1042.23', 'first-page': '1044', 'article-title': 'Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.', 'volume': '2', 'year': '1982', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. (1982)
  24. {'key': '2021111320181458000_5.6.1042.24', 'first-page': '1813', 'article-title': 'Differential activity of a tissue-specific extinguisher locus in hepatic and nonhepatic cells.', 'volume': '9', 'year': '1989', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Differential activity of a tissue-specific extinguisher locus in hepatic and nonhepatic cells. (1989)
  25. 10.1016/0092-8674(88)90429-1
  26. 10.1002/j.1460-2075.1988.tb03000.x / EMBO J. / Two distinct factors interact with the promoter regions of several liver-specific genes. (1988)
  27. 10.1038/342749a0
  28. 10.1016/S0021-9258(18)32436-0 / J. Biol. Chem. / Characterization of nonactivated and activated glucocorticoid-receptor complexes from intact rat thymus cells. (1983)
  29. 10.1002/j.1460-2075.1987.tb02573.x / EMBO J. / GCN4, a eukaryotic transcriptional activator protein, binds as a dimer to target DNA. (1987)
  30. 10.1016/0092-8674(90)90067-O
  31. 10.1038/294217a0
  32. 10.1101/gad.1.2.133
  33. 10.1016/S0092-8674(88)90449-7
  34. 10.1016/0092-8674(84)90507-5
  35. 10.1016/0092-8674(86)90762-2
  36. 10.1073/pnas.87.24.9838
  37. Kuo, C.J., Mendel, D.B. Hansen, L.P. and Crabtree. G.R. 1991. Independent regulation of HNF-1a and HNF-1b by retinoic acid in F9 teratocarcinoma cells. EMBO J. (in press). (10.1002/j.1460-2075.1991.tb07759.x)
  38. 10.1101/gad.4.8.1427
  39. 10.1101/gad.2.7.786
  40. 10.1126/science.3289117
  41. 10.1016/0092-8674(86)90507-6
  42. {'key': '2021111320181458000_5.6.1042.42', 'first-page': '141', 'article-title': "Isolement experimental du mesenchyme propre du foie et role morphogene de la composante mésodermique dans l'organogenese hépatique.", 'volume': '12', 'year': '1964', 'journal-title': 'J. Embryol. Exp. Morphol.'} / J. Embryol. Exp. Morphol. / Isolement experimental du mesenchyme propre du foie et role morphogene de la composante mésodermique dans l'organogenese hépatique. (1964)
  43. 10.1016/0012-1606(68)90092-4
  44. {'key': '2021111320181458000_5.6.1042.44', 'first-page': '427', 'article-title': 'An experimental analysis of liver development.', 'volume': '53', 'year': '1975', 'journal-title': 'Med. Biol.'} / Med. Biol. / An experimental analysis of liver development. (1975)
  45. 10.1126/science.2711183
  46. Maniatis, T., E.F. Fritsch, and J. Sambrook. 1982. Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
  47. 10.1016/0092-8674(90)90808-R
  48. 10.1016/0092-8674(89)90682-X
  49. 10.1016/0092-8674(90)90687-A
  50. 10.1016/S0021-9258(19)35442-0 / J. Biol. Chem. / Purification and characterization of nuclear factor III (origin recognition protein C), a sequence-specific DNA binding protein required for efficient initiation of adenovirus DNA replication. (1988)
  51. {'key': '2021111320181458000_5.6.1042.51', 'first-page': '747', 'article-title': 'Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter.', 'volume': '9', 'year': '1989', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Octamer transcription factors 1 and 2 each bind to two different functional elements in the immunoglobulin heavy-chain promoter. (1989)
  52. 10.1084/jem.162.3.930
  53. 10.1101/gad.2.12b.1687
  54. {'key': '2021111320181458000_5.6.1042.54', 'first-page': '2132', 'article-title': 'Transcriptional-translational regulatory circuit in Saccharomyces cerevisiae which involves the GCN4 transcriptional activator and the GCN2 protein kinase.', 'volume': '8', 'year': '1988', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Transcriptional-translational regulatory circuit in Saccharomyces cerevisiae which involves the GCN4 transcriptional activator and the GCN2 protein kinase. (1988)
  55. 10.1016/0022-2836(88)90460-3
  56. 10.1016/0926-6585(66)90333-5
  57. 10.1038/341624a0
  58. 10.1016/0092-8674(81)90313-5
  59. {'key': '2021111320181458000_5.6.1042.59', 'first-page': '347', 'article-title': 'Hormonal induction of differentiation in teratocarcinoma stem cells: Generation of parietal endoderm by retinoic acid and dibutyrl cAMP.', 'volume': '347', 'year': '1980', 'journal-title': 'Cell'} / Cell / Hormonal induction of differentiation in teratocarcinoma stem cells: Generation of parietal endoderm by retinoic acid and dibutyrl cAMP. (1980)
  60. 10.1016/0092-8674(90)90589-7
  61. 10.1126/science.3175662
  62. 10.1126/science.2494701
  63. {'key': '2021111320181458000_5.6.1042.63', 'first-page': '725', 'article-title': 'The firefly luciferase gene: Structure and expression in mammalian cells.', 'volume': '7', 'year': '1987', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The firefly luciferase gene: Structure and expression in mammalian cells. (1987)
  64. 10.1038/341405a0
Dates
Type When
Created 18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited 3 years, 9 months ago (Nov. 13, 2021, 11:19 p.m.)
Indexed 3 weeks, 5 days ago (Aug. 6, 2025, 8:56 a.m.)
Issued 34 years, 3 months ago (June 1, 1991)
Published 34 years, 3 months ago (June 1, 1991)
Published Online 34 years, 3 months ago (June 1, 1991)
Published Print 34 years, 3 months ago (June 1, 1991)
Funders 0

None

@article{Mendel_1991, title={HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro.}, volume={5}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.5.6.1042}, DOI={10.1101/gad.5.6.1042}, number={6}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Mendel, D B and Hansen, L P and Graves, M K and Conley, P B and Crabtree, G R}, year={1991}, month=jun, pages={1042–1056} }