The 11th International Symposium on 3D Genomics

Mammalian cells activate diverse defense mechanisms in response to stresses. Nuclear
stress bodies (nSBs) are transient membrane-less organelles in primates that only
present in sensing severe stresses. Little is known on how their formation contributes
to cellular homeostasis or whether nSBs have any physiopathological roles. Here, we
report that nSB components, including Satellite ⅢI (SatⅢ) DNAs, SatⅢ RNAs (the
hall marker of nSBs) and 30 proteins, are assembled into a well-organized structure
within 3 hours in living cells. Remarkably, the activated SatⅢ heterochromatin loci
rapidly expand, resulting in adjacent gene activation, including the transcription
suppressor NFIL3 known to dampen proinflammatory cytokine production. Upon
stresses, NFIL3 loci were found within or close to nSB territory due to SatⅢ locus
expansion, which enhances NFIL3 chromatin accessibility and makes NFIL3 promoters
spatially more accessible to transcription factors newly recruited to nSBs. Human
peripheral blood mononuclear cell (PBMC)-derived macrophages under heat shock and
LPS stresses exhibited increased expression of SatⅢ and NFIL3, the latter of which
prevents the excessive expression of key inflammatory cytokines. Importantly, NFIL3
expression positively correlates with SatⅢ activation in PBMCs from septic patients,
which appears to be beneficial for patient survival. These findings unveil an unexpected
role of the highly organized nSBs in shaping local gene organization upon stresses, and
highlight a crucial role of nSBs in restraining acute inflammatory responses.

Nuclear stress bodies,SatⅢ,acute inflammatory responses,NFIL3,membrane-less organelles