Figure 3.

The direct and indirect epigenetic pathway. The figure represents two different routes through which an epigenetic factor can modify the epigenome leading to altered gene expression. Epigenetic effects exerted by an external factor or intrinsic environment can lead to direct and indirect effects on the epigenome. Green represents direct effects of an epigenetic factor and red represents indirect effects of an epigenetic factor. The direct pathway can operate in two different ways; namely Type1 and Type 2. In the Type 1 direct pathway, the epigenetic factor directly exerts an effect on the epigenetic enzymes such as DNMTs, HDACs, HATs, HMTs, HDMs, etc. such that there is an altered bioavailability of these enzymes in the cell. A Type 2 direct effect is when an epigenetic factor interferes with a biochemical pathway such that there is altered availability of a metabolite required for constituting an epigenetic tag. Both cases can result in aberrant or inadequate recruitment of epigenetic tags in a random fashion to non-specific promoters, ultimately establishing an altered epigenetic profile. In the indirect pathway, the epigenetic factor indirectly exerts an effect on the epigenome by first interfering with any signaling pathways of the cell. An acute exposure to the epigenetic factor can cause altered expression of growth factors, receptors, ion channels and so on resulting in non-homeostatic cellular processes. This in turn might lead to an altered status of transcriptional machinery (bound or unbound to the promoter/enhancer) and its bioavailability in a cell. A chronic exposure to the epigenetic factor might lead to retention of such state of transcriptional machinery (bound or unbound to the promoter/enhancer) causing altered gene expression as well as aberrant recruitment of epigenetic enzymes, leading to permanent addition or removal of epigenetic tags to specific promoter/enhancers. This consequently establishes an altered epigenetic profile.