Model. At basal, the NF-κB pathway, possibly through its repressor NFKB1 (p50/p50 homodimers), is involved in the recruitment of H3K9 methylases (HMT) at intronic L1Md enriched in NF-κB binding sites motifs, and apposition of the repressive histone mark H3K9me3. H3K9me3 “islands” into the body of transcribed genes may help the processing of RNAP II (RNAPol II) and transcript stability. Upon irradiation, loss of the TNF-α–NF-κB pathway leads to a loss of H3K9me3 at the intronic L1Md, gene repression, and transcript stability. This is prevented by prior TNF-α treatment.