Premature termination of transcription from the P1 promoter of the mouse c-myc gene.
Modulation of transcriptional elongation within the c-myc gene is thought to play a major role in determining levels of c-myc mRNA in both normal and tumor cells. A discrete site of blockage to transcriptional elongation has previously been localized at the 3' end of exon 1 of the mouse and human c-myc genes. We here identify an additional site of transcriptional attenuation that is located between the P1 and P2 promoters of the c-myc gene and that mediates premature termination of transcripts initiating from the P1 promoter. A 95-nucleotide DNA fragment derived from this region prematurely terminated transcription when placed downstream from the promoter of the H-2Kbm1 gene and assayed by expression in Xenopus oocytes. We also show that the previously identified attenuation signal in exon 1 of the mouse c-myc gene can mediate premature termination of P1-initiated transcripts. Premature termination of P1-initiated transcripts presumably increases transcription from the downstream P2 promoter; aberrant regulation of this termination may explain the increased use of the P1 promoter that is characteristic of certain tumors in which myc is overexpressed.
Wright
S
S
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Mirels
L F
LF
Calayag
M C
MC
Bishop
J M
JM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D005091:Exons; D005786:Gene Expression Regulation; D016259:Genes, myc; D005822:Genetic Vectors; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D015347:RNA Probes; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014981:Xenopus
D015347:RNA Probes