Figure 3.

A proposed model of how genome structure influences phenotypic consequence. (A) In the naïve state, all inflammatory cells are almost indistinguishable with regards to their transcriptional profiles and durable epigenetic changes have yet to take place. (B) Due to thermodynamic fluctuations, however, some cells become primed states transiently at various possible loci. Chromatin structural changes by means of external signals, for example NO as a paracrine signal, can favor a primed state with specific characteristics. (C) If cells encounter activation signals in this primed state, there is a high probability they will become a specific phenotype following activation. For example, pro-inflammatory primed cells become pro-inflammatory cells (and vice versa). On the other hand, owing to the intrinsic stochasticity of all transcription, primed cells can become the opposing phenotype (i.e. inflammatory or anti-inflammatory), although this probability is lower. Rectangular insets below cells diagrams is a representation of the chromatin changes which might occur at specific gene loci.