In addition to analyzing the ligand-mediated gene regulation we also clustered the BDNF and MeCh-regulated genes into significantly-populated GO-term (Figure 5C) and KEGG pathway groups (Figure 5D).
In addition to biological consequences of RBP-J-mediated regulation, we also sought to investigate molecular mechanisms by which RBP-J regulated M2 gene expression especially expression of Arg1 given its role as a critical M2 effector molecule and its drastic regulation by RBP-J at the protein level (Fig. 4A).
With regard to positive regulation, we also have observed that Mf-1 is able to block key histone modifications (e.g., H3K9Ac and H3K4Me3) in several positively-regulated endogenous target genes in α-23 cells (Wang and Yen, unpublished results).
Consistent with a role for SIRT1 in stress induced translation regulation, we also have demonstrated that SIRT1 interacts with eIF-2alpha, a translation initiation factor, to regulate stress induced translation control (Ghosh et al).
To confirm this negative regulation, we also conducted co-transfection analysis of the luciferase reporter gene activity in the presence of the exogenous SP-1 expression (Fig. 6D) or exogenous SP-3 expression (Fig. 6F).
Therefore, in addition to Bayesian inference for combinatorial regulation, we also consider here a naive approximation that estimates the probability of combinatorial regulation by the product of individual TF binding probabilities. Figure 10 shows ROC results and the corresponding histograms for the two different methods.
To test whether the increase by UO126 after 2 h was already caused by a counter-regulation, we also determined hepcidin mRNA levels after 30 and 60 min. Hepcidin mRNA increased 1.5±0.1-fold 1.5±0.1-fold after.8±0.2-fold after 60 min (n = 2, data not shown) suggesting that the observed effects were indeed direct effects.
Among other proteins involved in regulation, we also found ten kinases.
Since PPAR γ heterodimerizes with RXR for transcription regulation, we also tested the effect of 9-cis-retinoic acid, an agonist of RXR.
In addition to this novel pathway of AM regulation, we also confirmed hypoxic induction of endometrial AM expression, an effect previously demonstrated in other cell types (49, 50).
