Journal
CELL REPORTS
Volume 31, Issue 12, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.107795
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Funding
- U.S. National Institutes of Health
- National Heart, Lung, and Blood Institute [5P01HL105339, 5R01HL111759, 5P01HL114501, K25HL133599, K25HL140186]
- National Cancer Institute [1R35CA220523, 5P50CA127003, 1R35CA197449, 1U01CA190234, 5P30CA006516]
- National Institute of Allergy and Infectious Diseases [5R01AI099204]
- NVIDIA Foundation
- Norwegian Research Council
- Helse Sor-Ost
- University of Oslo through the Centre for Molecular Medicine Norway (NCMM)
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Sex differences manifest in many diseases and may drive sex-specific therapeutic responses. To understand the molecular basis of sex differences, we evaluated sex-biased gene regulation by constructing sample-specific gene regulatory networks in 29 human healthy tissues using 8,279 whole-genome expression profiles from the Genotype-Tissue Expression (GTEx) project. We find sex-biased regulatory network structures in each tissue. Even though most transcription factors (TFs) are not differentially expressed between males and females, many have sex-biased regulatory targeting patterns. In each tissue, genes that are differentially targeted by TFs between the sexes are enriched for tissue-related functions and diseases. In brain tissue, for example, genes associated with Parkinson's disease and Alzheimer's disease are targeted by different sets of TFs in each sex. Our systems-based analysis identifies a repertoire of TFs that play important roles in sex-specific architecture of gene regulatory networks, and it underlines sex-specific regulatory processes in both health and disease.
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