Fig. 2: Model of chromatin priming and its functional consequence for gene expression.

Priming of regulatory elements by TFs constitutes a form of chromatin memory for the control of stimulus-dependent gene expression (inspired by findings reported in [10, 101]). Left: primed regulatory element carrying activating histone modifications have a persistent increase in chromatin accessibility and a gain in h-TF, HMs and CRs as a result of previous activity (see Fig. 1, right). Upon re-stimulation, such as neuronal activation or inflammation, s-TF and ad-TF can be recruited to the primed regions at a faster rate and likely bind with stronger affinity to their target binding sites. A subset of h-TF could also remain associated [101]. The recruitment of s-TF leads to the activation of the primed regulatory element, an enhancer in this case, via recruitment of RNA pol II. The now activated regulatory element can engage in canonical or novel long-range interactions with the promoter of target genes [10] resulting in increased transcription [10, 101]. H3K4me1 and H3K27ac indicated in the figure have been associated with priming events in the brain [10, 91] but other histone modifications may contribute to the process. Also, while histone modifications have been associated with priming events, their functional contribution to gene expression has been recently challenged (see main text). The example provided here does not exclude additional functional consequences of chromatin memory in the brain.