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. 2023 Feb 15;614(7949):732–741. doi: 10.1038/s41586-023-05711-7

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article′s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article′s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 10 — a. Aggregate plot of average MRE11 CUT&RUN coverage (fragment depth per bp per peak) ± s.e.m. in KA-stimulated nuclei isolated from Mre11^KO/fl infected with either ΔCre-GFP virus (Control) or Cre-mCherry (Mre11 cKO) at MRE11 binding sites (17,084 sites). MRE11 binding sites were determined by the SEACR peak calling algorithm. IgG indicates the CUT&RUN signal from a nonspecific IgG control and represents the average IgG across both ΔCre-GFP and Cre conditions. MRE11 (n = 3 Cre and n = 3 ΔCre-GFP), IgG (n = 3 Cre and n = 3 ΔCre-GFP). 1 mouse per replicate. ***P < 2.2e-16. P values were calculated using unpaired, two-tailed Wilcoxon rank-sum tests. b. Integrative Genomics Viewer browser image displaying CUT&RUN signal for NPAS4, MRE11 (Cre or ΔCre), and IgG (Cre or ΔCre) in 2 h KA-stimulated nuclei at the Bdnf gene. c. Aggregate CUT&RUN signal for NPAS4, RAD50 and MRE11 in 0 h vs 2 h stimulated hippocampal tissue at NPAS4-binding sites. Each NPAS4-binding site is represented as a single horizontal line centered at the peak summit and extended out ± 1 kb. Intensity of color correlates with sequencing signal as indicated by the scale bar for each factor (0 to 50 read-depth normalization). MRE11(n = 2), RAD50 (n = 4), NPAS4 (n = 5). 3-5 mice pooled per replicate. d. Venn diagram of overlaps between binding sites of MRE11, RAD50 and NPAS4 in 2 h KA-stimulated neurons. Peaks for each factor were determined using the SEACR peak calling algorithm and represent peaks found reproducibly across replicates (2 of 2 MRE11 replicates, 3 of 4 RAD50 replicates, and 4 of 5 NPAS4 replicates). 3-5 mice pooled per replicate. e. Most significant motifs enriched in MRE11 CUT&RUN peaks (2 h KA-stimulated). Motif enrichment was performed on 1 kb peaks extended 500 bp up and downstream from the peak maxima. Notable motifs include the NPAS4/bHLH-PAS motif, the AP1 family, and CTCF motifs. f. Aggregate of average CUT&RUN coverage (fragment depth per bp per peak) ± s.e.m. at all regulatory elements, subset by quartiles of NPAS4 CUT&RUN signal.Q1 = 44,864 sites, Q4 = 7,378 sites. MRE11(0 h and 2 h, n = 2), RAD50 (0 h, n = 3), RAD50 (2 h, n = 4). ***P < 2.2e-16; **P = 5.78e-06. P values by unpaired, two-tailed Wilcoxon rank-sum tests. 3-5 mice pooled per replicate.