title: Transcriptional activation of the H-ferritin gene in differentiated Caco-2 cells parallels a change in the activity of the nuclear factor Bbf.
abstract: In this paper, we examine the mechanisms that regulate the expression of the heavy (H) ferritin subunit in the colon carcinoma Caco-2 cell line allowed to differentiate spontaneously in vitro. The differentiation process of these cells in continuous culture is accompanied by an accumulation of the mRNA coding for the apoferritin H chain. The analysis of Caco-2 subclones stably transfected with an H-chain promoter-chloramphenicol acetyltransferase (CAT) construct revealed that the mRNA increase is paralleled by an enhanced transcription of the H gene, driven by the -100 to +4 region of the H promoter. The H gene transcriptional activation seems to be a specific feature of differentiated Caco-2 cells, since the activity of other promoters did not change upon differentiation. The -100 to +4 region of the H promoter binds a transcription factor called Bbf (B-box binding factor); electrophoretic-mobility-shift-assay analyses showed that the retarded complex due to Bbf-H promoter interaction is significantly increased in the differentiated cells. We propose that the activation of H-ferritin gene expression may be associated with the establishment of a differentiated phenotype in Caco-2 cells, and that the H-ferritin gene transcriptional up-regulation is accompanied by a modification in the activity of the transcription factor Bbf.
mesh_terms: D001483:Base Sequence; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000502:physiology; D051699:Cyclic AMP Response Element-Binding Protein A; D004268:DNA-Binding Proteins / Q000502:physiology*; D029721:Drosophila Proteins; D005293:Ferritins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: C073555:CrebA protein, Drosophila; D051699:Cyclic AMP Response Element-Binding Protein A; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D005293:Ferritins