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. 2019 Jul 2;9:9526. doi: 10.1038/s41598-019-45457-9

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© The Author(s) 2019

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Knockdown of CTCF levels in ES cells results in decreased core-periphery network structure in subTADs around pluripotency genes. (A) Observed heatmap of Chromosome-Conformation-Capture-Carbon-Copy data around the Olig1 and Olig2 genes in ES cells. The three Olig1-Olig2 subTADs used in subsequent core-periphery analysis are outlined in green and labeled 1 (B,C), 2 (D,E), and 3(F,G). (B,D,F) Observed/Expected heatmaps of Olig1-Olig2 (B) subTAD 1, (D) subTAD 2, and (F) subTAD3 in two wild type ES cell replicates (to row) and two CTCF knock down ES cell replicates (bottom). (C,E,G) Core-periphery test statistic Q for (C) subTAD 1, (E) subTAD 2, and (G) subTAD3. (H) Observed heatmap of Chromosome-Conformation-Capture-Carbon-Copy data around the Sox2 gene in ES cells. The three Sox2 subTADs used in subsequent core-periphery analysis are outlined in green and labeled 1 (I,J), 2 (K,L), and 3(M-N). (I,K,M) Observed/Expected heatmaps of Sox2 (I) subTAD 1, (K) subTAD 2, and (M) subTAD3 in two wild type ES cell replicates (to row) and two CTCF knock down ES cell replicates (bottom). (J,L,N) Core-periphery test statistic Q for (J) subTAD 1, (L) subTAD 2, and (N) subTAD3. Core and periphery nodes are labeled under each heatmap.