PRJNA271828
PLZF modifies chromatin to restrain inflammatory signalling [ChIP-Seq] (mouse)
We identify a mechanism that limits the inflammatory response. Probing the responses of macrophages to the key sensory Toll-like receptors, we identify that the Broad-complex, Tramtrack and Bric-abrac/ poxvirus and zinc finger (BTB/POZ), transcriptional regulator promyelocytic leukemia zinc finger (PLZF) limits the expression of inflammatory gene products. In accord with this, PLZF-deficient animals express higher levels of potent inflammatory cytokines and mount exaggerated inflammatory responses to infectious stimuli. Temporal quantitation of inflammatory gene transcripts showed increased gene induction in the absence of PLZF. Genome-wide analysis of histone modifications distinguish that PLZF establishes basal activity states of early response genes to maintain immune homeostasis and limit damaging inflammation. We show that PLZF stabilizes a corepressor complex that encompasses histone deacetylase activity to control chromatin. Overall design: we performed a chromatin immunoprecipitation followed by sequencing (ChIP-Seq) experiment on samples of bone marrow-derived macrophages (BMDMs) from WT or Zbtb16-/- mice (C57/Bl6 background ) untreated or treated for 30 min with LPS (100 ng/mL). Those DNA samples DNA were immunoprecipitated with H3K4me3 or H3K27ac antibodies.