Gene-specific recruitment of positive and negative elongation factors during stimulated transcription of the MKP-1 gene in neuroendocrine cells.

MAP kinase phosphatase-1 (MKP-1) controls nuclear MAP kinase activity with important consequences on cell growth or apoptosis. MKP-1 transcription is initiated constitutively but elongation is blocked within exon 1. It is unclear how induction of MKP-1 is controlled.

The rate of c-fos transcription in vivo is continuously regulated at the level of elongation by dynamic stimulus-coupled recruitment of positive transcription elongation factor b.

In mammalian cells, multiple stimuli induce the expression of the immediate early gene c-fos. The specificity of c-fos transcriptional response depends on the activation of signaling protein kinases, transcription factors, and chromatin-modifying complexes but also on a regulated block to elongation in the first intron. Here we show by chromatin immunoprecipitation that finely tuned control of c-fos gene expression by distinct stimuli is associated with a dynamic regulation of transcription elongation and differential phosphorylation of the C-terminal domain of RNA polymerase II.

Map kinase phosphatase-1 gene expression and regulation in neuroendocrine cells.

Long-term cellular processes like proliferation, differentiation, and adaptive responses (e.g. neuronal plasticity) are initiated by the synthesis of immediate early gene (IEG) products which control the expression of late response genes.