Figure 1

Model depicting the existence of T cells in distinct chromatin states in transcriptional memory responsive genes that allow for rapid and robust gene induction in memory T cells. In response to viral infection, naïve T-cells rapidly expand into effector T-cells and subsequently contract to produce a small population of resting, long-lived memory T cells. These memory cells have the ability to express genes more rapidly and robustly than effector T-cells; a feature known as transcriptional memory (Tm). In this multi-layered model of transcriptional memory, we envisage a scenario whereby multiple epigenetic mechanisms, such as PTMs, histone variants, transcription factors, gene looping, localisation of genes within the nucleus, and the regulatory elements themselves, collectively contribute to the transcriptional memory response in T cells. In the above Figure, H3/H2A nucleosomes are represented by blue cylinders and repressive PTMs are red balls; H2AZ/H3.3 nucleosomes are represented by red cylinders and active PTMs are signified by green, purple or blue coloured balls. The active transcription complex (ATC) is signified by an orange oval and the active enhancer complex (AEC) by a tan oval, each representing transcription factors (TF), PKC-θ, LSD1, Pol II and other unidentified members which are bound to the promoter region/TSS (TSS signified by a yellow box) or enhancer region (signified by a green box). The purple oval represents the memory transcription factors (M-TF). The memory complex (MC) is signified by a red oval representing unidentified members and Pol II. The above Figure also depicts the formation of a chromatin loop following activation, which allows the enhancer to interact with promoter. The chromatin loop relocates to the nuclear periphery upon activation, were it remains in resting memory T cells.