Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals

作     者：Burman, Andreanna Garcia-Milian, Rolando Whirledge, Shannon 

作者机构：Yale Sch Med Dept Obstet Gynecol & Reprod Sci 310 Cedar StPOB 208063 New Haven CT 06520 USA Yale Sch Med Bioinformat Support Program Cushing Whitney Med Lib New Haven CT 06520 USA 

出 版 物：《HUMAN GENOMICS》 (人类染色体)

年 卷 期：2020年第14卷第1期

页      面：19-19页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS) [R00 ES022983] Albert McKern Scholar Award National Institute of Environmental Health Sciences [ZICES102445] Funding Source: NIH RePORTER 

主　　题：Gene expression array Gene ontology analysis Environmental chemical Gene-environment interaction Xenoestrogen 

摘      要：Background An individual s response to environmental exposures varies depending on their genotype, which has been termed the gene-environment interaction. The phenotype of cell exposed can also be a key determinant in the response to physiological cues, indicating that a cell-gene-environment interaction may exist. We investigated whether the cellular environment could alter the transcriptional response to environmental chemicals. Publicly available gene expression array data permitted a targeted comparison of the transcriptional response to a unique subclass of environmental chemicals that alter the activity of the estrogen receptor, xenoestrogens. Results Thirty xenoestrogens were included in the analysis, for which 426 human gene expression studies were identified. Comparisons were made for studies that met the predefined criteria for exposure length, concentration, and experimental replicates. The cellular response to the phytoestrogen genistein resulted in remarkably unique transcriptional profiles in breast, liver, and uterine cell-types. Analysis of gene regulatory networks and molecular pathways revealed that the cellular context mediated the activation or repression of functions important to cellular organization and survival, including opposing effects by genistein in breast vs. liver and uterine cell-types. When controlling for cell-type, xenoestrogens regulate unique gene networks and biological functions, despite belonging to the same class of environmental chemicals. Interestingly, the genetic sex of the cell-type also strongly influenced the transcriptional response to xenoestrogens in the liver, with only 22% of the genes significantly regulated by genistein common between male and female cells. Conclusions Our results demonstrate that the transcriptional response to environmental chemicals depends on a variety of factors, including the cellular context, the genetic sex of a cell, and the individual chemical. These findings highlight the importance o