A cis-Acting Element inthePromoter Region oftheMurine c-myc GeneIsNecessary forTranscriptional Block

Ablock toelongation oftranscription hasbeenshowntooccurwithin thefirst exonofthehumanandmurine c-mycgenes.Theextent ofthis block was found tovarywiththephysiological state ofcells, indicating that modulation ofthetranscriptional block can servetocontrol theexpression ofthis gene.Todetermine which sequencesarerequired incisforthetranscriptional block, we generated a series ofconstructs containing various portions ofmurine c-myc5'-flanking andexon1sequences.We established populations ofHeLaand CV-1cells stably transfected withthese constructs. Thetranscription start sites weredetermined bySlnuclease mapping analysis, andtheextent oftranscriptional block wasmeasured bynuclear run-ontranscription assays. Ourresults demonstrate that atleast twocis-acting elements arenecessaryforthetranscriptional block. A3' element was found tobelocated intheregion wheretranscription stopped andshowed features reminiscent of some termination sites found inprocaryotes. A5'element waspositioned between theP1andP2 transcription start sites. We recently demonstrated thattwonuclear factor-binding sites reside between P1andP2(C. Asselin, A.Nepveu, andK.B.Marcu,Oncogene 4:549-558, 1989). Removalofthemore 3'binding site abolished thetranscriptional block. Recentstudies suggest thattheexpression ofseveral eucaryotic genescanberegulated atthelevel oftranscriptionelongation. Nuclear run-ontranscription assays re