Fig. 4: FOXM1 overexpression restores a youthful chromatin accessibility profile through repression of AP-1. | Nature Communications

Fig. 4: FOXM1 overexpression restores a youthful chromatin accessibility profile through repression of AP-1.

From: FOXM1 expression reverts aging chromatin profiles through repression of the senescence-associated pioneer factor AP-1

Fig. 4

a Heatmaps showing the ATAC-seq peak signals restored by FOXM1 in neonatal, elderly and FOXM1-overexpressing (FOXM1 OE) elderly HDFs. Signal is restored from the elderly profile to the neonatal profile by either increasing (chromatin opens, left) or decreasing (chromatin closes, right) upon lentivirus-mediated FOXM1 overexpression, in elderly HDFs. b Comparison of HOMER-defined Known Motif Enrichment between opened and closed ATAC-seq peaks upon FOXM1 OE. Positive values represent enrichment in opened peaks (present in neonatal but not in control elderly HDFs), while negative values represent enrichment in closed peaks (not present in neonatal HDFs but present in control elderly HDFs). Colors highlight motifs TEAD TFs (purple), FOX TFs (red), and AP-1 complex TFs (green). p-value determined using a two-tailed a z-test, adjusted with Bonferroni-Dunn correction. Motifs with adjusted p-value < 0.05 with a black border, motifs with adjusted p-value ≥ 0.05 with a gray border. c Genomic tracks representing epigenetic features in the JUN locus. Candidate cis-regulatory elements with promoter-like signature from the ENCODE project are shown in yellow. The region subsequently tested in promoter reporter assays is shown in light yellow. FOXM1 binding sites at JUN promoter defined by ChIP-seq data from the ENCODE project are shown in orange. ATAC-seq signal in neonatal (blue) and elderly (red) HDFs showing that chromatin accessibility is kept during aging. Different shades represent different individuals. d–f Gene expression analysis of JUN (d, Control n = 3, siRNA n = 3, p-value = 0.0007), ATF3 (e, Control n = 5, siRNA n = 5, p-value = 0.0053) and FOS (f, Control n = 5, siRNA n = 5, p-value = 0.0768) by RT-qPCR in neonatal HDFs treated with siRNA against FOXM1. Each data point corresponds to a biological replicate equal to the mean of 3 technical replicates. **p-value ≤ 0.01; ***p-value ≤ 0.0001 by two-tailed unpaired Student’s t test. Values represent mean ± SD. Source data are provided as a Source Data file.

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