Long-term variations of AP-1 composition after CRH stimulation: consequence on POMC gene regulation

It has been shown previously that the CRH-induced POMC gene transcription i n the corticotroph cell line AtT-20 involves an increase in AP-1 DNA bindin g activity that remained elevated for at least 24 h, while induction of c-f os was transient. We showed here that there were dramatic changes in protei n components of AP-1 including an initial recruitment of the transcriptiona l activators c-Fos and Jun-B then of Fra-2 and Jun-D. Changes in AP-1 compo sition were concomitant with a decrease in POMC mRNA. Moreover, the presenc e of Fra-2/Jun-D dimers suppressed the CRH-induction of c-fos mRNA expressi on as well as c-Fos/Jun-B recruitment in AP-1 complexes, suggesting the exi stence of autoregulatory loops of AP-1 composition that involve complex int eractions between the different members of the Jun and Fos families. It is concluded that CRH stimulation of corticotroph cells involves successive re cruitment of activators and repressors, possibly contributing to prevent ov er expression of POMC. (C) 2001 Elsevier Science Ireland Ltd. All rights re served.