Fig. 8: Bivalent histone modifications switch the transcriptional status of Nrf2 in response to IR.

a Centered CUT&Tag peaks of H3K4me3 (±2 Kb of TSS) and H3K27me3 (gene body) in BMPR2⁺ and BMPR2− HSCs at homeostasis (D0) and D1 after 6.5 Gy of IR. b Circos plot showing the switching events across different histone modification (HM) statuses between BMPR2⁺ and BMPR2− HSCs. c Significantly enriched GO terms of genes with switched HM status from bivalent to H3K4me3-only. d CUT&Tag signals of H3K4me3 and H3K27me3 across Nrf2, showing its switched HM status from bivalent to H3K4me3-only. e Fold changes in gene expression levels in BMPR2⁺ and BMPR2⁻ HSCs at D0 and D1 after 6.5 Gy of IR. n = 4 biological repeats per group. f Fold change in CellROX levels in BMPR2⁺ and BMPR2⁻ HSCs derived from Nrf2⁺/⁺ and Nrf2−/− mice at D1 after 6.5 Gy of IR. n = 4 biological repeats per group. g, h Percentage and number of BMPR2⁺ and BMPR2⁻ HSCs from Nrf2−/− mice at D0 and D1 after 6.5 Gy of IR. n = 8 mice per group. i Number of CFUs formed by BMPR2⁺ and BMPR2− HSCs from Nrf2−/− mice at D0 and D1 after 6.5 Gy of IR. n = 3 biological repeats per group. j Schematic diagram of the molecular mechanisms by which the BMP4-BMPR2-NRF2 pathway regulates the radiation resistance of BM HSCs. Data shown are mean ± SEM. Statistical analyses were conducted using two-way ANOVA with multiple comparisons by Tukey’s test (e, g–i) and unpaired two-sided Student’s t test (f). Source data are provided as a Source Data file.