Dominant genomic structures: Detection and potential signal functions in the interferon-beta domain

Enhanceosome Formation over the Beta Interferon Promoter Underlies a Remote-Control Mechanism Mediated by YY1 and YY2

“…These observations and early findings from our laboratory, which have shown the influence of this region on the induction of IFN-␤ (20), led to the identification of HS1-to HS3-associating factors (19).…”

“…Sites HS2 and HS3 flanked a register of six nucleosomes that are positioned in the absence of gene activity. Site HS1 marks a site next to the region of increased scaffold/matrix association potential (19).…”

“…SIDD profiles have been calculated according to an algorithm developed by Benham et al (5) as described previously (18). In a preceding study (19), we screened sequences far upstream from the beta interferon gene for candidate sites with regulatory potential. The coincidence of these signals with DNase I hypersensitive sites suggested that stress-induced secondary DNA structures have a signal function.…”

“…Basically, the SIDD algorithm (http://genomics.ucdavis.edu/benham/sidd/index .php) predicts the propensity of a DNA base pair to undergo strand separation under superhelical tension as it arises, due to tracking proteins or the loss of nucleosomes (19). To this end, the incremental free energy [G(x)] needed to separate the base pair at each position x is computed in the context of a defined stretch of DNA.…”

“…It is suggested that shortly after infection, two molecules of YY1 bound at positions Ϫ90 and Ϫ122 mediate the recruitment of GCN5 and initiate nucleosome sliding via histone hyperacetylation. However, while there exist two proximal YY1 sites in the murine regulatory region, no corresponding functional sites were found for the human counterpart (19). The detection of two far-upstream YY1 sites for both the human IFN-␤ (huIFN-␤) gene (positions Ϫ2000 and Ϫ3000) and the murine IFN-␤ (muIFN-␤) gene (positions Ϫ2700 and Ϫ4700) has further complicated this situation (19).…”