(Cell 159, 1665–1680; December 11, 2014) Our paper analyzed the three-dimensional (3D) architecture of genomes at high resolution in nine human and murine cell lines. One of our main conclusions was that the vast majority of loops are anchored at CTCF/cohesin-binding sites whose motifs are oriented in a convergent fashion, i.e., the motifs point at one another. We arrived at this conclusion by analyzing peaks where the two corresponding peak loci each contained a single CTCF-binding motif. We performed this analysis in eight different cell lines. It has come to our attention that, in this analysis, we inadvertently used the wrong peak file for one of the eight cell lines (GM12878). In addition to peaks in which there was a unique motif at each of the two peak loci, this file, which had been generated by a preliminary version of our code, included peaks whenever there was (1) a unique motif at one peak locus and (2) a unique motif on the opposite strand at the other peak locus. We have now redone the analysis using the correct file. As a result, we found that several numbers on page 1675 of the main text and page S73 of the Extended Experimental Procedures, as well as Figure 6D , need to be adjusted as shown below. The correct list of motifs associated with each loop anchor, together with their orientations, has been uploaded to the Gene Expression Omnibus (GEO) at the original accession number for the paper, GEO: GSE63525. These corrections do not affect the numbers for the other seven cell lines and do not modify the conclusions of the paper in any way. The main text corrections from page 1675 are shown below, with the correct numbers underlined and the original text numbers in brackets. “If CTCF sites were randomly oriented, one would expect all four orientations to occur equally often. But when we examined the 2,857 [4,322] peaks in GM12878 where the two corresponding peak loci each contained a single CTCF-binding motif, we found that the vast majority (90% [92%]) of motif pairs are convergent (Figures 6D and 6E). Overall, the presence, at pairs of peak loci, of bound CTCF sites in the convergent orientation was enriched 102-fold over random expectation (Extended Experimental Procedures). The convergent orientation was overwhelmingly more frequent than the divergent orientation, despite the fact that divergent motifs also lie on opposing strands: in GM12878, the counts were 2,574-10 [3,971-78] (257-fold [51-fold] enrichment, convergent versus divergent); in IMR90, 1,456-5 (291-fold); in HMEC, 968-11 (88-fold); in K562, 723-2 (362-fold); in HUVEC, 671-4 (168-fold); in HeLa, 301-3 (100-fold); in NHEK, 556-9 (62-fold); and in CH12-LX, 625-8 (78-fold). This pattern suggests that a pair of CTCF sites in the convergent orientation is required for the formation of a loop. The observation that looped CTCF sites occur in the convergent orientation also allows us to analyze peak loci containing multiple CTCF-bound motifs to predict which motif instance plays a role in a given loop. In this way, we can associate nearly two-thirds of peak loci (8,325 [8,175] of 12,903, or 64.5% [63.4%]) with a single CTCF-binding motif. The specific orientation of CTCF sites at observed peaks provides evidence that our peak calls are biologically correct. Because randomly chosen CTCF pairs would exhibit each of the four orientations with equal probability, the near-perfect association between our loop calls and the convergent orientation could not occur by chance (p < 10-1,185 [10-1,900], binomial distribution).” The Extended Experimental Procedures corrections from page S73 are shown below, with the correct numbers underlined and the original text numbers in brackets. “Out of 2857 [4322] peaks where we could localize both anchors down to unique motifs, we observed that 2574 (90%) [3971 (92%)] of the peaks contained a pair of motifs in a convergent orientation…” “…In this manner, we localized 1334 [1184] peak loci to unique CTCF motifs in GM12878. In total, we were able to localize 8325 [8175] of 12903 GM12878 peak loci to unique motifs.” A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin LoopingRao et al.CellDecember 11, 2014In BriefUsing 3D genome sequencing, we find ∼10,000 DNA loops across the human genome. Loop anchors typically occur at domain boundaries and bind CTCF in a convergent orientation, with the asymmetric motifs “facing” one another. On the inactive X chromosome, large loops are anchored at CTCF-binding repeats. Loops are conserved across cell types and species. Full-Text PDF Open Archive