ACUTE PHASE-DEPENDENT CHANGES IN THE BINDING OF RAT-LIVER NUCLEOPROTEINS TO THE CYTOKINE RESPONSE ELEMENT OF THE RAT HAPTOGLOBIN GENE

Hormones released during the acute phase reaction promote the transcri ptional activation of the haptoglobin (Hp) gene and a consequent incre ase of Hp protein synthesis in the liver. The mechanisms underlying th e alterations of basal transcription rates of eukaryotic genes are ass umed to result from modulations of the binding affinities between nucl eoproteins and specific DNA sequences in the enhancer and promoter ele ments. In order to characterize the changes in the interaction of nucl eoproteins with the promoter that accompany the induction of the Hp ge ne, nuclear extracts from normal and inflamed livers were probed with hormone responsive element (HRE) of the rat Hp gene by gel mobility sh ift and Southwestern assays. Each of the three cis-acting sequences of the HRE, elements A, B, and C, recognized a distinct set of proteins. Together they conferred an additional level of specificity to the pro tein binding sites of the entire ABC-element. These sites were recogni zed by proteins in liver nuclear extracts isolated from both control a nd treated rats. The differences in the gel shift and Southwestern pat terns of the corresponding DNA-protein complexes suggested that transc riptional activation of the Hp gene relied on changes in the concentra tions and/or functional modifications of preexisting proteins rather t han on the induction of new trans-acting factors.