title: Mechanisms of dietary response in mice and primates: a role for EGR1 in regulating the reaction to human-specific nutritional content.
abstract: BACKGROUND
  Humans have a widely different diet from other primate species, and are dependent on its high nutritional content. The molecular mechanisms responsible for adaptation to the human diet are currently unknown. Here, we addressed this question by investigating whether the gene expression response observed in mice fed human and chimpanzee diets involves the same regulatory mechanisms as expression differences between humans and chimpanzees.
  
  
  RESULTS
  Using mouse and primate transcriptomic data, we identified the transcription factor EGR1 (early growth response 1) as a putative regulator of diet-related differential gene expression between human and chimpanzee livers. Specifically, we predict that EGR1 regulates the response to the high caloric content of human diets. However, we also show that close to 90% of the dietary response to the primate diet found in mice, is not observed in primates. This might be explained by changes in tissue-specific gene expression between taxa.
  
  
  CONCLUSIONS
  Our results suggest that the gene expression response to the nutritionally rich human diet is partially mediated by the transcription factor EGR1. While this EGR1-driven response is conserved between mice and primates, the bulk of the mouse response to human and chimpanzee dietary differences is not observed in primates. This result highlights the rapid evolution of diet-related expression regulation and underscores potential limitations of mouse models in dietary studies.
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Weng
authors.forename: Haiyang
authors.initials: H
authors.lastname: Hu
authors.forename: Augix Guohua
authors.initials: AG
authors.lastname: Xu
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
authors.forename: Mehmet
authors.initials: M
authors.lastname: Somel
mesh_terms: D000818:Animals; D004032:Diet; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D002679:Pan troglodytes; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1