Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 280, Issue 13, Pages 13171-13178Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M414120200
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Earlier studies showed that HepG2 cells stably transfected with any one fibrinogen chain cDNA enhanced the expression of the other two fibrinogen chains. In this report, a regulatory element TGCTCTC in the gamma-fibrinogen promoter region, -322 to -316, is identified, which is involved in increased expression of gamma chain in HepG2 cells that are transfected with B beta fibrinogen cDNA. By electrophoretic mobility shift assay, three DNA-protein complexes were found to form with the regulatory element. The amount of the protein complexes that bind with the regulatory element was much reduced in HepG2 cells transfected with B beta cDNA. By DNA-affinity chromatography, mass spectrometry, and supershift assay, human heterogeneous nuclear ribonucleoprotein A1 ( hnRNP A1) was identified as a component of the complexes. Overexpression of hnRNP A1 suppressed basal gamma-fibrinogen transcription. These results indicate that the basal expression of gamma-fibrinogen is regulated by a constitutive transcriptional repressor protein, hnRNP A1, and the decreased binding activity of hnRNP A1 leads to the overexpression of gamma chain in HepG2 cells that overexpress the B beta chain.
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