A calcium-dependent switch in a CREST-BRG1 complex regulates activity-dependent gene expression.
CREST plays a critical role in activity-dependent development, but its mechanism of action is not well understood. Here, we show that a CREST-BRG1 complex regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-fos promoter is inhibited by BRG1-dependent recruitment of a phospho-Rb-HDAC repressor complex. Upon calcium influx, Rb becomes dephosphorylated at serine 795 by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CBP, suggesting that this mechanism may be generally involved in regulating calcium-dependent transcription of neuronal genes.
Qiu
Zilong
Z
Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0366, USA.
Ghosh
Anirvan
A
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000378:metabolism*; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D051381:Rats; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection / Q000379:methods; D020798:Two-Hybrid System Techniques
D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; C481041:Ss18l1 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D006655:Histone Deacetylases; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D002118:Calcium