Supplementary Figure 3: Recurrent deletions at a TAD boundary on chromosome X are associated with IRS4 dysregulation in different cancer types.

Related to main Figure 3. A genomic region near IRS4 (a gene transcribed from the (-) strand of the reference genome), highlighted in yellow, exhibiting clustered transcription factor binding sites is highlighted in gray. Each SCNA is accompanied with the depicted expression fold change of IRS4 (shown adjacent to each SCNA). Samples harboring the cis deletion, but not samples without the cis deletion, exhibit H3K27ac chromatin marks at IRS4 as well as at the candidate CRE nearby (highlighted in grey; asterisks indicate significant differential H3K27ac marks between carriers and non-carriers). 4C-Seq experiments using the candidate CRE as a viewpoint clearly demonstrate physical interaction with IRS4; a similar intensity in interaction was observed in samples harboring the cis deletion as in samples lacking the deletion. And also 4C-Seq experiments using the gene as a viewpoint show interaction between IRS4 and the putative CRE in both deletion carriers and non-carriers. LUSC samples S00086, S00473 and S00166 were verified, using semi-quantitative RT-PCR, to exhibit high-level upregulation of IRS4, whereas S00478 and S00198 showed merely baseline-level expression (data not shown). For all remaining carrier and non-carrier samples, we verified outlier and non-outlier expression, respectively, by qPCR (Supplementary Table 3).