Transcription of the INF-
is
initiated as a result of viral infection via a well-defined and
ordered series of steps. Formation of the enhaceosome complex is
the key to control of transcription in response to environmental cues.
Control of transcription is achieved via concerted
combinatorial and synergistic
action of activators, as depicted in the above figure.
Viral-induced expression of Interferon is believed to occur via the following
ordered steps:
Within four hours of viral infection, several activators bind to a
65 base-pair long, nucleosome-free "enhancer" region of chromatin,
upstream of the core promoter.
NF-
B and IRF-1 bind first, followed by
ATF-2, IRF-3 and c-Jun, and finally IRF-7. The binding of these species
occurs cooperatively with the HMG-I(Y) architectural factor.
The assembled nucloprotein complex subsequently recruits Gcn5 histone acetylase, which acetylates histones in the neighboring nucleosome, as well as the Lys-71 residue of the HMG-I(Y), thereby stabilizng the enhanceosome complex. The stable enhanceosome then recruits the CREB binding protein (CPB), and the RNA Pol II complex. This is followed by recruitment of the SWI/SNF complex, which remodels the chromatin by loosening the nucleosome over the core promoter region, allowing the TFIID transcription factor access to the gene, and switching on transcription.
Eventually, CPB acetylates the Lys-65 residue of the HMG-I(Y), disrupting the enhanceosome, and terminating transcription.
Refrences: