Sex Differences in Gene Expression and Regulatory Networks across 29 Human Tissues - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Cell Reports Year : 2020

Sex Differences in Gene Expression and Regulatory Networks across 29 Human Tissues

Abstract

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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hal-03642288 , version 1 (06-05-2022)

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Camila Lopes-Ramos, Cho-Yi Chen, Marieke Kuijjer, Joseph Paulson, Abhijeet Sonawane, et al.. Sex Differences in Gene Expression and Regulatory Networks across 29 Human Tissues. Cell Reports, 2020, 31 (12), pp.107795. ⟨10.1016/j.celrep.2020.107795⟩. ⟨hal-03642288⟩
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