RT Journal Article
SR Electronic
T1 Understanding Tissue-specific Gene Regulation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 110601
DO 10.1101/110601
A1 Abhijeet R. Sonawane
A1 John Platig
A1 Maud Fagny
A1 Cho-Yi Chen
A1 Joseph N. Paulson
A1 Camila M. Lopes-Ramos
A1 Dawn L. DeMeo
A1 John Quackenbush
A1 Kimberly Glass
A1 Marieke L. Kuijjer
YR 2017
UL http://biorxiv.org/content/early/2017/08/11/110601.abstract
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.