Preferred Label : IFN-Beta Enhancer Pathway;
NCIt related terms : The information-processing pathway at the IFN-beta enhancer;
Alternative definition : BIOCARTA: 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. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_pcafpathway;
Origin ID : C39183;
UMLS CUI : C1512581;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
