The role of putative intragenic control elements in c-fos regulation by calcium and growth factor signalling pathways.

Abstract:

:Sequences in the transcribed region of the c-fos gene have been suggested to control c-fos induction following exposure of cells to mitogens or stimuli that increase intracellular calcium concentrations. Using a mutational analysis we show that putative regulatory elements present in the first intron of the human c-fos gene and the fos-intragenic-regulatory-element (FIRE) are not required for c-fos regulation by growth factor and calcium signalling pathways in AtT20 and PC12 cells. Removal of the c-fos first intron and the FIRE did not increase the basal level of c-fos mRNA and only moderately reduced the magnitude of calcium-induced transcription mediated by either the entire c-fos promoter or the cAMP response element (CRE). Intragenic mutations did not affect serum response element (SRE)-dependent gene expression induced by calcium signals but caused a superinduction of c-fos expression in nerve growth factor-stimulated PC12 cells. These results indicate that c-fos promoter elements, rather than intragenic sequences, are the principal targets of transcription-regulating signalling pathways. This suggests that CRE- and SRE-bound activators of transcription initiation may also enhance, in a signal-dependent manner, c-fos transcript elongation beyond promoter-proximal pause sites.

journal_name

J Neurochem

authors

Lange CM,Bading H

doi

10.1046/j.1471-4159.2001.00342.x

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

1293-300

issue

5

eissn

0022-3042

issn

1471-4159

journal_volume

77

pub_type

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