Abstract
The liver-enriched transcription factor CCAAT/enhancer binding protein (C/EBP) binds to numerous liver-specific promoters, yet the mechanism by which the protein stimulates transcription has not been described. The serum albumin promoter, which is liver specific, contains a strong C/EBP-binding site tightly juxtaposed to a binding site for the ubiquitous factor nuclear factor-Y (NF-Y). The binding of C/EBP impairs the binding of NF-Y; yet surprisingly, this arrangement leads to strong synergistic activation of a minimal promoter in liver nuclear extracts. Transcriptional synergism is manifested by NF-Y facilitating the ability of C/EBP to form preinitiation complexes that are stable through multiple rounds of transcription. Binding by itself, C/EBP stimulates transcription weakly without forming stable complexes, and moving the NF-Y binding site 10 bp away from the C/EBP site increases NF-Y binding in the presence of C/EBP but reduces the efficiency of stable complex formation and transcriptional synergism. These findings show that C/EBP requires precise positioning next to a ubiquitous factor for optimal formation of stable complexes and provides a model to understand the dramatic activation of the albumin gene in hepatic development.
References
55
Referenced
102
10.1101/gad.1.3.256
10.1101/gad.3.8.1146
10.1073/pnas.84.19.6673
10.1101/gad.5.9.1538
10.1038/345361a0
10.1242/dev.113.1.217
/ Development / Hepatocyte differentiation initiated during endodermal-mesenchymal interaction prior to liver formation. (1991)10.1016/0092-8674(87)90036-5
10.1101/gad.2.8.957
10.1073/pnas.85.21.7937
10.1126/science.1899487
10.1016/0092-8674(91)90531-3
10.1101/gad.4.9.1541
10.1126/science.2943018
10.1016/0092-8674(89)90877-5
10.1101/gad.4.8.1416
10.1016/0092-8674(88)90109-2
10.1016/0092-8674(86)90519-2
10.1016/0092-8674(88)90119-5
10.1016/S0021-9258(17)39577-7
/ J. Biol. Chem. / Separation and partial characterization of three functional steps in transcription initiation by human RNA polymerase II. (1985)10.1016/S0021-9258(18)61372-9
/ J. Biol. Chem. / Functional steps ininitiation and reinitiation from the major late promoter in a HeLa nuclear extract. (1987){'key': '2021111320224972000_6.6.991.21', 'first-page': '4750', 'article-title': 'The rat albumin promoter is composed of six distinct positive elements within 130 nucleotides.', 'volume': '9', 'year': '1989', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / The rat albumin promoter is composed of six distinct positive elements within 130 nucleotides. (1989)10.1073/pnas.86.5.1553
10.1002/j.1460-2075.1990.tb07509.x
/ EMBO J. / Co-evolution from yeast to mouse: cDNA cloning of the two NF-Y (CP-1/CBF) subunits. (1990)10.1016/S0092-8674(88)80011-4
10.1016/0092-8674(88)90118-3
10.1101/gad.1.2.133
10.1073/pnas.83.16.5889
10.1126/science.3289117
10.1016/0092-8674(87)90583-6
10.1016/0092-8674(91)90321-O
10.1038/345359a0
10.1101/gad.2.5.528
{'key': '2021111320224972000_6.6.991.33', 'first-page': '773', 'article-title': 'Extracellular signals that regulate liver transcription factors during hepatic differentation in vitro.', 'volume': '11', 'year': '1991', 'journal-title': 'Mol. Cell. Biol.'}
/ Mol. Cell. Biol. / Extracellular signals that regulate liver transcription factors during hepatic differentation in vitro. (1991)10.1126/science.2711183
10.1073/pnas.87.14.5378
10.1016/0092-8674(90)90808-R
10.1073/pnas.87.10.3992
10.1101/gad.4.10.1714
10.1073/pnas.88.1.224
10.1002/j.1460-2075.1987.tb04854.x
/ EMBO J. / Discrete elements within the SV40 enhancer region display different cell-specific enhancer activities. (1987)10.1038/333040a0
10.1002/j.1460-2075.1984.tb02164.x
/ EMBO J. / Tissue-specific expression is conferred by a sequence from the 5′ end of the rat albumin gene. (1984)10.1101/gad.1.10.1172
10.1101/gad.1.3.268
10.1016/0092-8674(90)90459-R
10.1073/pnas.85.3.757
10.1016/S0021-9258(18)61506-6
/ J. Biol. Chem. / Factors involved in specific transcription in mammalian RNA polymerase II. Functional analysis of initiation factors IIA and IID and identification of a new factor operating at sequences downstream of the initiation site. (1987)10.1146/annurev.bi.59.070190.003431
10.1101/gad.1.1.65
10.1038/319121a0
10.1073/pnas.79.17.5254
10.1126/science.2683088
10.1101/gad.5.9.1553
10.1016/0022-2836(90)90341-I
10.1073/pnas.85.23.9076
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, 11:24 p.m.) |
Indexed | 3 months, 1 week ago (May 22, 2025, 5:30 a.m.) |
Issued | 33 years, 2 months ago (June 1, 1992) |
Published | 33 years, 2 months ago (June 1, 1992) |
Published Online | 33 years, 2 months ago (June 1, 1992) |
Published Print | 33 years, 2 months ago (June 1, 1992) |
@article{Milos_1992, title={A ubiquitous factor is required for C/EBP-related proteins to form stable transcription complexes on an albumin promoter segment in vitro.}, volume={6}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.6.6.991}, DOI={10.1101/gad.6.6.991}, number={6}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Milos, P M and Zaret, K S}, year={1992}, month=jun, pages={991–1004} }