TRANSCRIPTION ELONGATION OF THE MURINE ORNITHINE DECARBOXYLASE (ODC) GENE IS REGULATED IN-VITRO AT 2 DOWNSTREAM ELEMENTS BY DIFFERENT ATTENUATION MECHANISMS

Ornithine decarboxylase (ODC) plays an important role in cell prolifer ation. Its expression is tightly regulated at the mRNA and protein lev els and is found to be deregulated in various malignancies. The rapid acid dramatic induction of cellular ODC mRNA upon serum addition raise d the possibility that a transcriptional attenuation mechanism may be involved in the regulation of ODC gene expression, Using transcription in HeLa nuclear extract acid isolated transcription complexes, we hav e identified two sites of transcription arrest downstream to the trans cription start site: Attenuator 1 (Att.1) located at +220, near two re peats of a USF/ Myc-Max binding consensus sequence and attenuator 2 (A tt.2) located at +1590 near a long stretch of T-residues, The two atte nuators exhibit distinct properties as revealed by elongation of brief ly initiated and partially purified transcription complexes: Att.l ser ves as transient pause site while arrest at Att,2 is more prolonged. T he arrest at both attenuators is modulated by the general elongation f actor TFIIS. In a promoter independent transcription system, using par tially purified RNA polymerase II, only Att.2 was recognized efficient ly. This suggests that the recognition of Att.2 is an intrinsic proper ty of the polymerase while Att.1 recognition has to be facilitated by an auxiliary factor/s.