Fig. 1

A potential role of activated nSBs in monocytic cells. At times of perturbed cellular processes induced by infections (e.g., TLR2 activation), oxidative stress, chemicals, and/or heat shock, the 13–17 SAT III loci across the human genome open up and rapidly expand in size within 1–2 h. Early during the activation, HSF1 is activated to bind HSEs in the SAT III loci to induce the production of SAT III RNA by RNA Polymerase II, and this process continues to expand the size of the nSB core. The produced SAT III RNA cores recruit HSF1 proteins and then other proteins that make up the outer layers of nSBs, all of which promote the robust expansion of nSBs close to target genes. This expansion effectively allows the transcription factors and splicing factors in nSBs, including HSF1, to act on a number of target DNA loci. One of the target genes is NFIL3, a gene that codes for a transcription activator and repressor protein with important functions in the immune system. The NFIL3 gene is transcribed, in part, because of the nSB expansion. Elevated levels of NFIL3 lead to active suppression of the expression of lethal inflammatory mediators (e.g., TNFα, IL-1β, and IL-8) in cells, particularly monocytic cells. Suppression of these inflammatory mediators at the systemic level has the potential to decrease the mortality of patients with sepsis and other systemic inflammatory conditions