Journal Article

SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation

Piechaczyk, M, Bossis, G, Vives, E, Tempé, D, Brockly, F, Brooks, H, De Rossi, S

2014

Overview

The inducible proto-oncogenic (c-Fos:c-Jun)/AP-1 transcription complex binds 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) in its target genes. It is tightly controlled at multiple levels to avoid the deleterious effects of its inappropriate activation. In particular, SUMOylation represses its transactivation capacity in transient reporter assays using constitutively expressed proteins. This led to the presumption that (c-Fos:c-Jun)/AP-1 SUMOylation would be required to turn-off transcription of its target genes, as proposed for various transcription factors. Instead, thanks to the generation of an antibody specific for SUMO-modified c-Fos, we provide here direct evidence that SUMOylated c-Fos is present on a stably integrated reporter TPA-inducible promoter at the onset of transcriptional activation and colocalizes with RNA polymerase II within chromatin. Interestingly, (c-Fos:c-Jun)/AP-1 SUMOylation limits reporter gene induction, as well as the appearance of active transcription-specific histone marks on its promoter. Moreover, non-SUMOylatable mutant (c-Fos:c-Jun)/AP-1 dimers accumulate to higher levels on their target promoter, suggesting that SUMOylation might facilitate the release of (c-Fos:c-Jun)/AP-1 from promoters. Finally, activation of GADD153 , an AP-1 target gene, is also associated with a rapid increase in SUMOylation at the level of its TRE and c-Fos SUMOylation dampens its induction by TPA. Taken together, our data suggest that SUMOylation could serve to buffer transcriptional activation of AP-1 target genes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Publishing Group [1987-....]
• Subject: 631/208/200 / 631/337/458/538 / 692/699/67/395 / Acetic acid / Activator protein 1 / Apoptosis / Base Sequence / c-Fos protein / c-Jun protein / Cancer / Cell Biology / CHOP protein / Chromatin / DNA-directed RNA polymerase / Gene expression / Genes / Genetic aspects / Genetic transcription / Health aspects / HEK293 Cells / Histones / Human Genetics / Humans / Internal Medicine / JNK Mitogen-Activated Protein Kinases - metabolism / Life Sciences / Medicine / Medicine & Public Health / Oncogenes / Oncology / Promoter Regions, Genetic / Promoters / Protein Binding / Protein Transport / Proto-Oncogene Proteins c-fos - metabolism / Reporter gene / RNA polymerase / RNA Polymerase II - metabolism / RNA, Small Interfering - genetics / short-communication / Signal transduction / Small Ubiquitin-Related Modifier Proteins - metabolism / SUMO protein / Sumoylation / Transcription activation / Transcription Factor AP-1 - metabolism / Transcription factors / Transcription, Genetic / Transcriptional Activation