Transcriptional elongation of c-myb is regulated by NF-kappaB (p50/RelB).
High levels of c-myb expression are necessary for the proliferation of hematopoietic precursor cells whereas down-regulation of c-myb is required for terminal differentiation; this down-regulation occurs through a conditional block to transcriptional elongation in intron I. We previously observed that cAMP analogs prevented the late down-regulation of c-myb during hexamethylene bisacetamide (HMBA)-induced differentiation of murine erythroleukemia (MEL) cells and blocked differentiation; this correlated with the induction of NF-kappaB (p50/RelB) complexes which were shown to bind to NF-kappaB recognition sites flanking the transcriptional pause site of c-myb. We now selected stably-transfected MEL cells which overexpressed p50, RelB or both at levels similar to those induced by cAMP to determine whether these NF-kappaB proteins regulate c-myb expression in intact cells. We demonstrate that transcriptionally active NF-kappaB (p50/RelB) complexes, but not p50 or RelB alone, prevented the early and late down-regulation of c-myb mRNA and increased c-myb transcriptional elongation in HMBA-induced MEL cells. The increase in c-myb expression was sufficient to block erythroid differentiation and allow continuous proliferation of cells in the presence of HMBA. Steady-state c-myb mRNA levels in untreated cells were not affected by overexpression of NF-kappaB, suggesting that p50/RelB specifically modulated the efficiency of transcriptional attenuation during MEL cell differentiation.
Suhasini
M
M
Department of Medicine and Cancer Center, University of California, San Diego, La Jolla, California, CA 92037-0652, USA.
Pilz
R B
RB
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D020570:Genes, myb; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D016328:NF-kappa B