Home LiteratureArticle Details
PMID: 1694011 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Hepatic transcription of the acute-phase alpha 1-inhibitor III gene is controlled by a novel combination of cis-acting regulatory elements.

Molecular and cellular biology ·Vol. 10 ·No. 7 ·1990-07-00 ·Pages 3483-91

Abraham LJ, Bradshaw AD, Shiels BR, Northemann W, Hudson G, Fey GH

Abstract

mRNA coding for the abundant broad-range plasma proteinase inhibitor alpha 1-inhibitor III (alpha 1I3) was detected only in rat liver, while mRNA for the related proteins alpha 1-macroglobulin and alpha 2-macroglobulin was also found in a variety of nonhepatic tissues. cis-Acting control elements necessary for the hepatic transcription of alpha 1I3 were mapped by transfection and expression studies of control-region constructs in cultured hepatic and nonhepatic cells. The promoter-proximal 5'-flanking region contained four control elements, I to IV, located between -109 and -196 base pairs upstream of the transcriptional start site relevant for the hepatic transcription of this gene. Elements II and III were essential, and I and IV exerted strong modulatory effects. Elements I to III acted as positive regulators, and IV acted as a negative element. Element II contained the sequence TGGCA and is probably a binding site for a nuclear factor related to the known transcription factor NF1. The other three elements did not resemble consensus binding sites for known transcription factors that are involved in the hepatocyte-specific transcription of other well-characterized plasma protein genes, such as the prototype factor HNF-1. Thus, the alpha 1I3 gene achieves its highly hepatocyte-specific transcription through a novel combination of cis-acting control elements and trans-acting factors.

MeSH Terms
Acute-Phase Proteins/genetics Animals Base Sequence Cell Line Chromosome Deletion Female Genes Genes, Regulator Humans Liver/metabolism Luciferases/genetics,metabolism Male Molecular Sequence Data Organ Specificity Promoter Regions, Genetic Protease Inhibitors/metabolism RNA, Messenger/genetics Rats Recombinant Fusion Proteins/metabolism Transcription, Genetic Transfection alpha-Macroglobulins/genetics
Chemicals
Acute-Phase Proteins Protease Inhibitors RNA, Messenger Recombinant Fusion Proteins alpha 1-inhibitor 3 alpha-Macroglobulins Luciferases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Abraham L J
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Bradshaw A D
Shiels B R
Northemann W
Hudson G
Fey G H
References (51)
51 references, click to expand
  1. Characterization and hepatic expression of rat alpha 1-inhibitor III mRNA.
    J Biol Chem. 1988 Mar 15;263(8):4013-22 PMID: 2450089
  2. Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte-specific promoters.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):7937-41 PMID: 2460858
  3. Tissue-specificity of liver gene expression: a common liver-specific promoter element.
    Nucleic Acids Res. 1988 Apr 25;16(8):3165-74 PMID: 2453838
  4. Expression of rat alpha 2-macroglobulin gene during pregnancy.
    J Biochem. 1986 Oct;100(4):989-93 PMID: 2434464
  5. Identification and sequencing of cDNA clones for the rodent negative acute-phase protein alpha 1-inhibitor 3.
    Eur J Biochem. 1987 Apr 15;164(2):375-81 PMID: 2436907
  6. Sequence of rat liver alpha 2-macroglobulin and acute phase control of its messenger RNA.
    J Biol Chem. 1987 Jan 5;262(1):446-54 PMID: 2432068
  7. Three high molecular weight protease inhibitors of rat plasma. Isolation, characterization, and acute phase changes.
    J Biol Chem. 1987 Jan 5;262(1):438-45 PMID: 2432067
  8. Common evolutionary origin of alpha 2-macroglobulin and complement components C3 and C4.
    Proc Natl Acad Sci U S A. 1985 Jan;82(1):9-13 PMID: 2578664
  9. Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes.
    Mol Cell Biol. 1989 Apr;9(4):1415-25 PMID: 2786140
  10. Two different liver-specific factors stimulate in vitro transcription from the human alpha 1-antitrypsin promoter.
    EMBO J. 1988 Jul;7(7):2075-87 PMID: 3262058
  11. A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs.
    Nature. 1988 Jul 21;334(6179):218-24 PMID: 3398920
  12. A high-efficiency HeLa cell nuclear transcription extract.
    DNA. 1988 Jan-Feb;7(1):47-55 PMID: 3349904
  13. Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters.
    Science. 1987 Oct 30;238(4827):688-92 PMID: 3499668
  14. The interplay of DNA-binding proteins on the promoter of the mouse albumin gene.
    Cell. 1987 Dec 24;51(6):963-73 PMID: 3690666
  15. Factors involved in control of tissue-specific expression of albumin gene.
    Cell. 1987 Aug 14;50(4):627-38 PMID: 3607880
  16. Tissue-specific in vitro transcription from the mouse albumin promoter.
    Cell. 1986 Dec 5;47(5):767-76 PMID: 3779841
  17. The human beta-interferon gene enhancer is under negative control.
    Cell. 1986 May 23;45(4):601-10 PMID: 3708688
  18. Rapid and efficient site-specific mutagenesis without phenotypic selection.
    Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92 PMID: 3881765
  19. DNA-mediated gene transfer into adult rat hepatocytes in primary culture.
    Mol Cell Biol. 1990 Feb;10(2):689-95 PMID: 2105458
  20. Sertoli cell synthesizes and secretes a protease inhibitor, alpha 2-macroglobulin.
    Biochemistry. 1990 Jan 30;29(4):1063-8 PMID: 1692734
  21. Genomic sequencing.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 PMID: 6326095
  22. Characterization of rat ribosomal DNA. The highly repetitive sequences that flank the ribosomal RNA transcription unit are homologous and contain RNA polymerase III transcription initiation sites.
    J Mol Biol. 1984 Mar 25;174(1):141-62 PMID: 6716475
  23. Sequencing end-labeled DNA with base-specific chemical cleavages.
    Methods Enzymol. 1980;65(1):499-560 PMID: 6246368
  24. The TGGCA-binding protein: a eukaryotic nuclear protein recognizing a symmetrical sequence on double-stranded linear DNA.
    Nucleic Acids Res. 1984 May 25;12(10):4295-311 PMID: 6328417
  25. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing.
    Gene. 1984 Jun;28(3):351-9 PMID: 6235151
  26. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen.
    Science. 1980 Jul 25;209(4455):497-9 PMID: 6248960
  27. Expression of differentiated functions in hepatoma cell hybrids: high frequency of induction of mouse albumin production in rat hepatoma-mouse lymphoblast hybrids.
    Proc Natl Acad Sci U S A. 1974 Mar;71(3):927-31 PMID: 4362639
  28. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
  29. The acute phase response of the liver in inflammation.
    Prog Liver Dis. 1990;9:89-116 PMID: 1690438
  30. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection.
    Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777-81 PMID: 6294651
  31. Several distinct "CCAAT" box binding proteins coexist in eukaryotic cells.
    Proc Natl Acad Sci U S A. 1988 Feb;85(3):757-61 PMID: 3422457
  32. The role of cis-acting promoter elements in tissue-specific albumin gene expression.
    Science. 1989 Apr 21;244(4902):343-6 PMID: 2711183
  33. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication.
    Cell. 1987 Jan 16;48(1):79-89 PMID: 3024847
  34. Hormonal regulation and tissue-specific localization of alpha 2-macroglobulin in rat ovarian follicles and corpora lutea.
    Endocrinology. 1989 Dec;125(6):2985-95 PMID: 2479532
  35. Human apolipoprotein CIII gene expression is regulated by positive and negative cis-acting elements and tissue-specific protein factors.
    J Biol Chem. 1988 May 15;263(14):6857-64 PMID: 2834395
  36. Recombinant interleukin 6 regulates the transcriptional activation of a set of human acute phase genes.
    J Biol Chem. 1988 Sep 5;263(25):12554-8 PMID: 2457587
  37. Cell type-specific expression of the human apoB gene is controlled by two cis-acting regulatory regions.
    J Biol Chem. 1988 Aug 15;263(23):11452-8 PMID: 3165376
  38. Firefly luciferase gene: structure and expression in mammalian cells.
    Mol Cell Biol. 1987 Feb;7(2):725-37 PMID: 3821727
  39. High affinity binding site for nuclear factor I next to the hepatitis B virus S gene promoter.
    EMBO J. 1986 Aug;5(8):1967-71 PMID: 3463507
  40. A nonchromatographic assay for expression of the chloramphenicol acetyltransferase gene in eucaryotic cells.
    Anal Biochem. 1986 Jul;156(1):251-6 PMID: 3461723
  41. Structure and negative transcriptional regulation by glucocorticoids of the acute-phase rat alpha 1-inhibitor III gene.
    Biochemistry. 1989 Jan 10;28(1):84-95 PMID: 2495816
  42. Sequence and acute phase regulation of rat alpha 1-inhibitor III messenger RNA.
    J Biol Chem. 1988 Mar 15;263(8):3999-4012 PMID: 2831216
  43. Type 1 plasminogen activator inhibitor gene: functional analysis and glucocorticoid regulation of its promoter.
    Proc Natl Acad Sci U S A. 1988 Aug;85(15):5525-9 PMID: 2840665
  44. Two distinct factors interact with the promoter regions of several liver-specific genes.
    EMBO J. 1988 Jun;7(6):1711-9 PMID: 2844524
  45. Transcriptional control of the mouse prealbumin (transthyretin) gene: both promoter sequences and a distinct enhancer are cell specific.
    Mol Cell Biol. 1986 Dec;6(12):4697-708 PMID: 3025666
  46. Purification of a NF1-like DNA-binding protein from rat liver and cloning of the corresponding cDNA.
    EMBO J. 1988 Oct;7(10):3115-23 PMID: 3053160
  47. Heterogeneous lobular distribution of hepatocytes expressing acute-phase genes during the acute inflammatory reaction.
    J Exp Med. 1989 Jul 1;170(1):349-54 PMID: 2473162
  48. The alpha-macroglobulin bait region. Sequence diversity and localization of cleavage sites for proteinases in five mammalian alpha-macroglobulins.
    J Biol Chem. 1989 Sep 25;264(27):15781-9 PMID: 2476433
  49. Interaction of a hepatoma-specific nuclear factor with transcription-regulatory sequences of the human alpha-fetoprotein and albumin genes.
    Mol Cell Biol. 1988 Dec;8(12):5179-87 PMID: 2468995
  50. Structure and acute-phase regulation of the rat alpha 2-macroglobulin gene.
    Biochemistry. 1988 Dec 27;27(26):9194-203 PMID: 2468362
  51. Fine-structure mapping of the three mouse alpha-fetoprotein gene enhancers.
    Mol Cell Biol. 1988 Mar;8(3):1169-78 PMID: 2452972
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1990-07-00
Pages
3483-91
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360783
Subset
IM
Grants
FIC NIH HHS · 1 FO5 TW04073-01 · United States
NIAID NIH HHS · AI22166 · United States
NIAID NIH HHS · AI23351 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]