Extended Data Figure 5. Comparison of miR-221 and miR-222 and effects of miR221/222 deletion on the transcriptional response to LPS.

a, Alignment of the mature miR-221 and miR-222 sequences. The miRNA seed sequence is highlighted in yellow. b, Venn diagram displaying overlap between Microcosm target predictions for mmu-miR-221 and mmu-miR-222. c, Alignment and computational scores of miR-221 sequence with predicted Brg1 UTR target site. Alignment of miR-222 sequence with the site is also shown. d, Brg1 expression in BMDMs transfected with the given oligonucleotide (n=3 biologically independent samples). e, LPS-induced cytokine production in BMDMs transfected with given miRNA mimics, as measured by ELISA (n=5 biologically independent samples). f, Schematic of the miR-221/222 locus after targeting with a construct designed to generate both complete and conditional miR-221/222 knockout mice. g, Schematic of the miR-221/222 locus after breeding targeted mice (f) with EIIa-Cre mice, which results in complete deletion of miR-221/222. h, miRNA expression in BMDMs from littermates with a wildtype or miR-222 knockout allele (n=5 biologically independent samples). i, LPS-induced gene expression in naïve or tolerized peritoneal macrophages isolated from wildtype or miR-222 knockout littermates (n=7 biologically independent samples). j, Heatmap comparing the effect of Brg1/Brm knockdown¹⁵ and miR-222 knockout on gene expression. Colors represent values of the given ratios; red indicates increased expression, white indicates no change, and blue indicates decreased expression. k, Heat map of LPS-induced gene expression in wildtype and miR-222 knockout macrophages. For all bar graphs, mean +/− SEM is plotted. ** p < 0.01, * p < 0.05, + p < 0.1 as determined by two-sided Student’s t-test for paired (d-e) or heteroscedastic (i) values.