Two distinct mechanisms of transcriptional control operate on c-myc during differentiation of HL60 cells.
AUTOR(ES)
Siebenlist, U
RESUMO
We examined the mechanisms that control the downregulation of the c-myc mRNA during differentiation of HL60 cells. On treatment with dimethyl sulfoxide, HL60 cells downmodulated their steady-state c-myc message levels, ceased to proliferate, and underwent terminal differentiation. In nuclear run-on assays in which distinct segments of the c-myc gene were used as probes, an increased blocking to elongation of nascent c-myc transcripts was shown during the early phase of differentiation. During a later phase, however, a loss of transcriptional initiation was observed. This loss of promoter activity correlated well with dramatic changes in the chromatin structure of the c-myc gene, as determined by DNase I-hypersensitive site analysis. In particular, two hypersensitive sites near the two major c-myc promoters disappeared at the time that promotion abated. The newly described, later-acting negative transcriptional control of c-myc also correlated temporally with the inability to reverse the downregulation of the c-myc message quickly on withdrawal of the differentiating agent. Therefore, a terminal step during differentiation may be linked to the later-acting mode of transcriptional regulation of c-myc. The evidence presented in this report has implications for tumorigenesis in Burkitt lymphomas, in which the germ line, nontranslocated c-myc allele is transcriptionally silent.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=363218Documentos Relacionados
- Elongation and maturation of c-myc RNA is inhibited by differentiation inducing agents in HL60 cells.
- Induction of differentiation in HL60 cells by the reduction of extrachromosomally amplified c-myc.
- Transcriptional inactivation of c-myc and the transferrin receptor in dibutyryl cyclic AMP-treated HL-60 cells.
- c-myc gene inactivation during induced maturation of HL-60 cells. Transcriptional repression and loss of a specific DNAse I hypersensitive site.
- Transcriptional and post-transcriptional regulation of c-myc expression during the differentiation of murine erythroleukemia Friend cells.