A Prostate Cancer Risk Element Functions as a Repressive Loop that Regulates HOXA13  Zhifei Luo, Suhn Kyong Rhie, Fides D. Lay, Peggy J. Farnham  Cell Reports  Volume 21, Issue 6, Pages 1411-1417 (November 2017) DOI: 10.1016/j.celrep.2017.10.048 Copyright © 2017 The Authors Terms and Conditions

Cell Reports 2017 21, 1411-1417DOI: (10.1016/j.celrep.2017.10.048) Copyright © 2017 The Authors Terms and Conditions

Figure 1 Identification of the TAD Containing the Prostate Cancer Risk-Associated SNPs at 7p15.2 A 5-kb resolution chromatin contact probability map was generated for RWPE-1 cells; shown here is the region containing the risk SNPs located at 7p15.2 (the color key shows the Hi-C interaction frequency). The spot indicating interaction between the HOXA locus and the SNP-containing region is indicated by a green circle at the intersection of the line coming from the SNP region and the line coming from the HOXA locus. The colored bars show the different TADs called in each individual Hi-C replicate and in the merged replicate. Cell Reports 2017 21, 1411-1417DOI: (10.1016/j.celrep.2017.10.048) Copyright © 2017 The Authors Terms and Conditions

Figure 2 HOXA13 Is Upregulated upon Deletion of the 7p15.2 Risk Element (A) The bubble plot shows differential gene expression within ± 2 Mb of the 7p15.2 risk SNPs. The y axis indicates log2 fold change, and the green dashed lines show a 1.5-fold change without log transformation. The x axis indicates the distance between the transcription start site of each gene in the region and the risk SNPs. Genes with less than 1 transcript per million (TPM) in both control and deletion groups are labeled as “not expressed” (red dots); expressed genes are shown with blue dots. The dot size is scaled for relative TPM values. (B) An enlarged view of the HOXA cluster. Axes are as described in (A). Cell Reports 2017 21, 1411-1417DOI: (10.1016/j.celrep.2017.10.048) Copyright © 2017 The Authors Terms and Conditions

Figure 3 Comparison of Transcriptomic Changes upon Deletion of the 7p15.2 Risk Locus versus HOXA13 Overexpression (A) Shown is a list of commonly deregulated genes in deletion and HOXA13-overexpressing cells. All genes have at least a 1.5-fold change (adjusted p value < 0.05). Transcription factors are highlighted in bold. (B) Commonly altered canonical pathways in deletion versus overexpressing cells were identified using Ingenuity Pathway Analysis. Cell Reports 2017 21, 1411-1417DOI: (10.1016/j.celrep.2017.10.048) Copyright © 2017 The Authors Terms and Conditions