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Two distinct mechanisms of transcriptional control operate on c-myc during differentiation of HL60 cells.
Author(s) -
Ulrich Siebenlist,
Peter Bressler,
Kathleen Kelly
Publication year - 1988
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.8.2.867
Subject(s) - biology , downregulation and upregulation , chromatin , microbiology and biotechnology , cellular differentiation , carcinogenesis , transcriptional regulation , chromatin immunoprecipitation , gene expression , gene , promoter , cancer research , genetics
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.

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