Abstract:
:Alterations in expression of c-myb can have profound effects on the growth and differentiation of hematopoietic cells. Thus, it is important to understand the mechanisms by which c-myb is regulated during hematopoietic cell differentiation. Previous studies pertaining to the regulation of c-myb have been carried out with the avian and murine forms of the gene; the current studies were designed to determine the mechanisms of regulation of the human form of c-myb. Transcriptional analysis by nuclear run-on assays revealed that an attenuation of transcription was the means of primary regulation during retinoic acid- and vitamin D3-induced differentiation of HL-60 cells, while other mechanisms in addition to attenuation were active during dimethyl sulfoxide (DMSO)- and phorbol ester-induced differentiation. Densitometric analysis of the changes in c-myb transcription caused by phorbol ester suggested that the c-myb promoter may be down-regulated during phorbol ester-induced differentiation of HL-60. Additional studies exhibited post-transcriptional regulation by phorbol ester. DMSO was also shown to regulate c-myb at the post-transcriptional level. Interestingly, the post-transcriptional regulation of c-myb by DMSO required continuous transcription. This requirement was shared for c-myc but not ornithine decarboxylase expression. The transcriptional dependency of c-myb post-transcriptional regulation did not equate to translational dependency, thus a novel post-transcriptional regulatory mechanism may control c-myb gene expression. The multiple levels of regulation of c-myb suggest the importance of proper control for hematopoietic cell differentiation.
journal_name
Oncogenejournal_title
Oncogeneauthors
Boise LH,Gorse KM,Westin EHsubject
Has Abstractpub_date
1992-09-01 00:00:00pages
1817-25issue
9eissn
0950-9232issn
1476-5594journal_volume
7pub_type
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