Regulation of gamma-fibrinogen chain expression by heterogeneous nuclear ribonucleoprotein A1.

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 Bbeta 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 Bbeta 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 Bbeta chain.