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. 2014 Sep 29;3:161. Originally published 2014 Jul 11. [Version 2] doi: 10.12688/f1000research.4753.2

Figure 1. Involvement of IKKα in estrogen-triggered ER-dependent activation of the pS2 promoter.

Figure 1.

Upper panel: chromatin landscape and factors present at the pS2 (as known as TFF1) promoter in the presence of IKKα. The pS2 promoter is enriched with nucleosomes (blue and white cylinders) that dwell in positions proximal to the transcription start site (+1 position) and at ER binding sites. Only low levels of histone H3 lysine 9 dimethylation (H3K9me2) exist due to the space repulsion of histone methyltransferase from IKKα residing at the neighboring H3S10 site. RNA polymerase holoenzyme (Pol II) (yellow oval) is present at the proximal promoter region near the transcription start site (TSS, shown by black vertical line) of the pS2 gene. Lower panel: chromatin landscape and factors present at pS2 promoter following IKKα knockdown or IKKα inhibitor BAY11-7082 treatment. Once levels of IKKα have decreased, ER recruits the histone methyltransferase Suv39H1 or demethylase LSD1 proteins to bind within the pS2 promoter. Once the LSD1 is activated and demethylates its target H3K9me2, it generates reactive oxygen species (ROS) to cause DNA damage effects including base oxidation and nicks results from DNA damage itself and related DNA repair. In sum, the inhibition of IKKα results in the reversion of estrogen triggered anti-apoptotic effects to pro-apoptotic effects.