Abstract
Changes in expression of the c-myc proto-oncogene during the response of cells to growth or differentiation are often mediated at the transcriptional level, including control of the rates of initiation and elongation. Regulation of the level of initiation and elongation of c-myc gene transcription is likely to be mediated by the interaction of specific proteins with regulatory elements near or within the gene. Both positive and negative regulatory elements have been identified for the murine c-myc gene (Remmers et.al. 1986; Bentley and Groudine, 1988). To elucidate the mechanisms involved in negative control of c-myc transcription, we have employed the WEM 231 early B lymphoma cell line as a model system, since a major component of regulation of c-myc gene expression in these murine cells occurs at the level of transcription. Proliferation of WEHI 231 cells can be arrested within 24–48 hours following incubation with an antiserum against the expressed surface Ig, such as a goat anti-mouse Ig preparation (GaMIg) (McCormack et. al. 1984) or by treatment with phorbol ester (Levine et.al. 1986). Previously we demonstrated that a selective 5- to 10- fold decrease in c-myc mRNA expression occurs within 24 hours of treatment; this drop correlated with a decrease in the transcription of the c-myc gene (Levine et. al. 1986). We reasoned that control of this decreased rate of transcription could relate either to increased factor binding to a negative element or decreased binding to a positive element. In either case, a change in binding might be apparent. Here we report on the mapping of changes in the complex interaction of proteins at two sites within the c-myc locus during the down modulation of c-myc gene transcription in growth arrested WEHI 231 cells. The sequences mediating this binding are interacting with proteins within the NF-KB family of factors, implicating these factors in the regulation of c-myc gene transcription.
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© 1990 Springer-Verlag Berlin Heidelberg
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Duyao, M.P., Kessler, D.J., Spicer, D.B., Sonenshein, G.E. (1990). Binding of NF-KB-like Factors to Regulatory Sequences of the c-myc Gene. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1990. Current Topics in Microbiology and Immunology, vol 166. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75889-8_27
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DOI: https://doi.org/10.1007/978-3-642-75889-8_27
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