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Having identified the genes differentially regulated by context we used IPA software to identify canonical pathways that are significantly over-represented among them.
In the tibiae from WT-OVX, ERα−/− and WT-SN mice, 440, 439 and 987 genes respectively were differentially regulated by context alone compared to WT.
Of the genes differentially regulated by context compared to WT, the majority (76%) of the 172 genes common to ERα−/− and WT-SN tibiae were up-regulated.
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In addition, REST and CoREST expression and function are tightly regulated by context-specific transcriptional and post-transcriptional mechanisms including bidirectional feedback loops with various ncRNAs.
The findings here suggest that Ape1 ssAP and dsAP endonuclease activities are regulated by sequence context and the relative concentrations of certain chemical elements in vivo, and that Ape1 incision activity occurs on complex replication, recombination, and/or transcription DNA intermediates.
The activity of TANs is regulated by behavioral context, exhibiting pauses of several hundred milliseconds following presentation of salient sensory stimuli [18], [19].
GTP-loading of Arf6 is stimulated by several families of GEFs and is presumably regulated by cellular context and via activation of signalling pathways in response to differing stimuli.
In cells, enzymes of both classes are further regulated by their spatial context and kinases are often tethered to subcellular structures such as membranes or occur as parts of immobile scaffolding complexes.
Further differentiation will then depend on the availability of LSTFs, which is regulated by the cell-context dependent amount and type of LSTFs, Id and Hes proteins (Fig. 12A).
Accordingly, it is possible that RUNX3 can either suppress or activate Wnt signaling activity by binding to the TCF4/β-catenin complex, and the direction of Wnt signaling modulation may be regulated by a cell context-dependent mechanism.
Rbm15 has been identified as a factor necessary for X-chromosome inactivation27, which is a representative context regulated by Polycomb silencing.
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