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. 2024 Mar 7;15:1781. doi: 10.1038/s41467-024-45773-3

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© The Author(s) 2024

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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Fig. 4 — A Heatmaps of active and repressive marks in the chromatin of WT mice ( ± 2 kb of Kdm1a peaks). B Distribution of Kdm1a peaks between chromatin compartments. C Schematic illustration of CTCF connection in upDEGs. D Density plots showing ChIP-seq signal for H3K27ac, H3K27me3 and H3K4me3 in CTCF loops associated with upDEGs in hippocampal chromatin of control and Kdm1a-ifKO mice. Four graphs are presented for each hPTM corresponding to (i) ±5 kb window centered on the CTCF peaks directly linked to the upDEGs; (ii) upDEGs metagene; (iii) metagene for the CTCF-loop associated genes; and (iv) ±5 kb window centered on the CTCF peaks directly linked to the upDEG-associated genes. Transcript levels in control and ifKO mice, and CTCF and Kdm1a density plots in WT hippocampal chromatin are also shown. E Genomic profiles and CTCF ChIA-PET interactions at the Spint1 locus (purple box). CTCF loops bring the H3K27me3-enriched Spint1 gene closer to active genes Vps18 and Ino80. The lower panels show H3K27ac levels in the chromatin of control and Kdm1a-ifKOs at Spint1 and neighbour genes linked through first and second-order CTCF connections. Vps18 and Ino80 show lower levels of H3K27ac in Kdm1a-ifKOs, in parallel to the increase for this hPTM in Spint1. The dashed line represents H3K27ac density in control mice. Transcript levels are shown in the yellow track. F 4C-seq interaction profiles using the Spint1 promoter as viewpoint (anchor). Interactome profiles were generated using the hippocampus of Kdm1a-ifKO (n = 3) and control mice (n = 3). Significant reduction in the interaction of Spint1 was observed with the gene body of Ino80 and with an intergenic region (in red), while a higher interaction frequency was observed with Gm33412 and Ankrd63 (in blue), which are also upregulated in Kdm1a-ifKO neurons. The position of upDEGs is indicated with black boxes; the tracks for H3K27me3 ChIP-seq and CTCF-ChIA-PET interactions are shown. G Volcano plot showing the most significant changes on interaction frequencies in the 4C-seq generated with Spint1 as viewpoint (likelihood ratio test, pval <0.1). Source data are provided as a Source data file.