| ALT_DEFINITION
| - The packaging of eukaryotic DNA into nucleosomes inhibits the access of factors to DNA and results in the repression of transcription, replication, and recombination. Local modification of histones on enhancers and promoters is required to activate gene expression. The transcription factors that bind to nucleosome-free regions of DNA or to DNA within nucleosomes recruit two types of enzymatic activities that modify the surrounding chromatin architecture. Chromatin remodeling machines, such as SWI/SNF complex, alter the structure of the pronucleosome in an ATP-dependent manner, and often cause nucleosome sliding. The second type of chromatin modifying complexes recruited by transcription factors covalently modify the N-terminal tails of histones by adding or removing phosphate, methyl, or acetyl groups. Virus-induced transcription of the human interferon-beta gene illustrates one of the best-characterized examples of the mechanisms by which the information contained in the DNA is transferred to the histone-N termini by generating novel adhesive surfaces required for the recruitment of transcription complexes. Upon virus infection, the gene is switched on by three transcription factors (NF-kB, IRFs, and ATF-2/c-Jun), and an architectural protein (HMG I(Y)), all of which bind cooperatively to the nucleosome-free enhancer DNA to form an enhanceosome. The enhanceosome targets the modification and repositioning of a nucleosome that blocks the formation of a transcriptional preinitiation complex on the IFN-beta promoter. This is accomplished by the ordered recruitment of HATs, SWI/SNF, and basal transcription factors. Initially, the PCAF HAT-containing complex is recruited, and it acetylates the nucleosome. This is followed by the recruitment of the CBP-PolII holoenzyme complex. The bromodomain containing transcription complexes SWI/SNF and TFIID are recruited to the promoter via bivalent interactions between the enhanceosome and specifically acetylated histone N termini. More specifically, acetylation of H4 lysine 8 is required for recruitment of the SWI/SNF complex, whereas acetylation of lysines 9 and 14 in histone H3 is critical for the recruitment of the general transcription factor TFIID. An unknown kinase recruited by the enhanceosome phosphorylates H3 Ser 10, a prerequisite for H3K14 acetylation by PCAF. The SWI/SNF remodeling machine arrives at the promoter via bivalent interactions with CBP and the acetylated histone N tails. SWI/SNF alters the structure of the nucleosome, thus allowing recruitment and DNA binding of TFIID to the TATA box. The DNA bending induced upon TFIID binding to the promoter causes sliding of the SWI/SNF-modified nucleosome to a new position 36 bp downstream, thus allowing the initiation of transcription. This cascade is obligatory for IFN-beta gene activation.BIOCARTA
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