REPRESSION OF THE H5 HISTONE GENE BY A FACTOR FROM ERYTHROCYTES THAT BINDS TO THE REGION OF TRANSCRIPTION INITIATION

Expression of histone H5, like that of other erythrocyte specific proteins, declines during the latter stages of erythroid maturation because of a decrease in the rate of gene transcription. Here, we report the isolation of cIBR (chicken initiation binding repressor), a 75 kDa DNA binding glycoprotein from mature chicken erythrocytes that recognizes sequences spanning the transcription start sites of the H5 gene. cIBR was found to repress transcription from the H5 promoter in vitro and this effect could be relieved by mutations that lowered the affinity of the factor for its cognate sequence. cIBR inhibited transcription by interfering with assembly of the initiation complex, but it did not affect transcription from pre-assembled complexes. Consistent with this, binding of bacterially expressed human TFIID to the TATA element prevented subsequent binding of cIBR, although the opposite was not true. This, and the fact that cIBR had no effect when bound in a location upstream from the promoter, suggests that binding of cIBR to the start site region causes repression by direct interference with general transcription factors other than TFIID, possibly TFIIB. cIBR was found in mature and relatively late erythrocytes but not in early erythroid cells which actively transcribe the H5 gene; the transcriptionally active cells contain instead cIBF (chicken initiation binding factor). Purified cIBF is a non-glycosylated 68-70 kDa DNA binding protein(s) which also recognizes the region of transcription initiation of the H5 gene.