title: Mitogenic activation of normal T cells leads to increased initiation of transcription in the c-myc locus.
abstract: Early following mitogenic activation, normal human T cells express elevated levels of steady-state mRNAs encoding the nuclear-localized protooncogenes, c-fos, c-myc, and c-myb. Although the mechanisms responsible for increases in these specific mRNAs are not known, recent evidence suggests that up-regulation of c-myc could result from the release of a nascent chain elongation block. Run-on transcription analyses of c-myc show here that increased initiation and not modulation of elongation efficiency is largely responsible for elevated c-myc mRNA levels in activated T cells. Transcriptional stimulation of c-myc commences from a chromatin state that appears poised for activation. As determined by DNase I hypersensitive site analyses, the chromatin structure of c-myc in resting T cells resembles that of other cell types expressing high levels of c-myc, and furthermore, no changes in hypersensitive sites can be correlated with mitogenic stimulation of c-myc transcription. Because mitogen-induced up-regulation and terminal differentiation-associated down-regulation of c-myc are mechanistically different, it appears that c-myc is subject to a variety of distinct transcriptional controls. In addition to c-myc, c-fos and c-myb are shown to be induced via a transcriptional mechanism in T cells.
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000187:drug effects; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2