Topologically associating domain underlies tissue specific expression of long intergenic non-coding RNAs

Accumulating evidence indicates that long intergenic non-coding RNAs (lincRNAs) show more tissue-specific expression patterns than protein-coding genes (PCGs). However, although lincRNAs are subject to canonical transcriptional regulation like PCGs, the molecular basis for the specificity of their expression patterns remains unclear. Here, using expression data and coordinates of topologically associating domains (TADs) in human tissues, we show that lincRNA loci are significantly enriched in the more internal region of TADs compared to PCGs and that lincRNAs within TADs have higher tissue specificity than those outside TADs. Based on these, we propose an analytical framework to interpret transcriptional status using lincRNA as an indicator. We applied it to hypertrophic cardiomyopathy data and found disease-specific transcriptional regulation: ectopic expression of keratin at the TAD level and derepression of myocyte differentiation-related genes by E2F1 with down-regulation of LINC00881. Our results provide understanding of the function and regulation of lincRNAs according to genomic structure.