PT - JOURNAL ARTICLE AU - Abhijeet R. Sonawane AU - John Platig AU - Maud Fagny AU - Cho-Yi Chen AU - Joseph N. Paulson AU - Camila M. Lopes-Ramos AU - Dawn L. DeMeo AU - John Quackenbush AU - Kimberly Glass AU - Marieke L. Kuijjer TI - Understanding Tissue-specific Gene Regulation AID - 10.1101/110601 DP - 2017 Jan 01 TA - bioRxiv PG - 110601 4099 - http://biorxiv.org/content/early/2017/08/11/110601.short 4100 - http://biorxiv.org/content/early/2017/08/11/110601.full AB - Although all human tissues carry out common processes, tissues are distinguished by gene expres-sion patterns, implying that distinct regulatory programs control tissue-specificity. In this study, we investigate gene expression and regulation across 38 tissues profiled in the Genotype-Tissue Expression project. We find that network edges (transcription factor to target gene connections) have higher tissue-specificity than network nodes (genes) and that regulating nodes (transcription factors) are less likely to be expressed in a tissue-specific manner as compared to their targets (genes). Gene set enrichment analysis of network targeting also indicates that regulation of tissue-specific function is largely independent of transcription factor expression. In addition, tissue-specific genes are not highly targeted in their corresponding tissue-network. However, they do assume bottleneck positions due to variability in transcription factor targeting and the influence of non-canonical regulatory interactions. These results suggest that tissue-specificity is driven by context-dependent regulatory paths, providing transcriptional control of tissue-specific processes.