Transcription of Fos family genes in nucleus accumbens: roles of AP-1, epigenetics, and stochasticity.

We elaborate upon further details of the mechanisms involved in transcription of Fos family and other immediate early genes in brain. The AP-1 element on the cfos promoter is bound by homodimers of Jun family proteins and heterodimers of Jun family members with Fos family members including ∆FosB. The frequencies of combinations are discussed, as well as their activities, which may be activating or inhibiting. With acute stimulation by psychostimulants the mRNAs of cfos and fosB are induced within a few minutes to rise to maximum levels in about 30 minutes with a decline to basal levels in a few hours. The many possible mechanisms for the shutdown are discussed. Epigenetic modifications are strongly implicated in the instigation and inhibition of transcription, particularly histone modifications which may decompactify DNA. Summaries of histone modifications have been related to a histone code. Various general schemes for the steps to transcription have been proposed and three of these are described, followed by more detailed dynamical pictures. Finally, results for transcription measurements in single cells are discussed and some simple mathematical models that have been employed to quantify their stochastic properties are described.