In carcinoma cell lines, the ERK2 signaling reduces the levels of H3.1/H3.2 by suppressing CHAF1B transcription, thus creating the “space” for gap-filling with H3.3, leading to a HIRA-dependent H3.3 enrichment at the promoter of EMT, resulting in tumor progression and metastasis formation. The gene discussed is CHAF1B; the disease is neoplasm.