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Abstract：
Chronic stress threatens an individual\'s capacity to maintain psychological and physiological homeostasis, but the molecular processes underlying the biological embedding of these experiences are not well understood. This is particularly true for marginalized groups, presenting a fundamental challenge to decreasing racial, economic, and gender-based health disparities. Physical and social environments influence genome function, including the transcriptional activity of core stress responsive genes. We studied the relationship between social experiences that are associated with systemic inequality (e.g., racial segregation, poverty, and neighborhood violence) and blood cell (leukocytes) gene expression, focusing on the activation of transcription factors (TF) critical to stress response pathways. The study used data from 68 women collected from a convenience sample in 2013 from the Southside of Chicago. Comparing single, low-income Black mothers living in neighborhoods with high levels of violence (self-reported and assessed using administrative police records) to those with low levels of violence we found no significant differences in expression of 51 genes associated with the Conserved Transcriptional Response to Adversity (CTRA). Using TELiS analysis of promoter TF-binding motif prevalence we found that mothers who self-reported higher levels of neighborhood stress showed greater expression of genes regulated by the glucocorticoid receptor (GR). These findings may reflect increased cortisol output from the hypothalamic-pituitary-adrenal (HPA) axis, or increased GR transcriptional sensitivity. Transcript origin analyses identified monocytes and dendritic cells as the primary cellular sources of gene transcripts up-regulated in association with neighborhood stress. The prominence of GR-related transcripts and the absence of sympathetic nervous system-related CTRA transcripts suggest that a subjective perception of elevated chronic neighborhood stress may be associated with an HPA-related defeat-withdrawal phenotype rather than a fight-or-flight phenotype. The defeat-withdrawal phenotype has been previously observed in animal models of severe, overwhelming threat. These results demonstrate the importance of studying biological embedding in diverse environments and communities, specifically marginalized populations such as low-income Black women.
摘要：
慢性应激威胁到个体维持心理和生理稳态的能力,但是这些经历的生物嵌入背后的分子过程还没有得到很好的理解。对于边缘化群体来说尤其如此，给减少种族带来了根本性的挑战，经济,和基于性别的健康差距。物理和社会环境影响基因组功能，包括核心应激反应基因的转录活性。我们研究了与系统不平等相关的社会经验之间的关系(例如，种族隔离,贫穷,和邻里暴力）和血细胞（白细胞）基因表达，专注于对应激反应途径至关重要的转录因子（TF）的激活。该研究使用了2013年从芝加哥南区的便利样本中收集的68名女性的数据。比较单身，生活在暴力水平较高的社区的低收入黑人母亲（自我报告并使用行政警察记录进行评估）与暴力水平较低的黑人母亲，我们发现与逆境保守转录反应（CTRA）相关的51个基因的表达没有显着差异。使用TELiS对启动子TF结合基序患病率的分析，我们发现自我报告较高水平的邻里压力的母亲显示出糖皮质激素受体（GR）调节的基因表达更高。这些发现可能反映了下丘脑-垂体-肾上腺（HPA）轴的皮质醇输出增加，或增加GR转录敏感性。转录物来源分析确定单核细胞和树突状细胞是与邻域应激相关上调的基因转录物的主要细胞来源。GR相关转录本的突出和交感神经系统相关CTRA转录本的缺乏表明，对慢性邻域压力升高的主观感知可能与HPA相关的失败-退出表型有关，而不是战斗或飞行表型。以前在严重的动物模型中观察到失败-戒断表型，压倒性的威胁。这些结果证明了在不同环境和社区中研究生物嵌入的重要性，特别是低收入黑人妇女等边缘化人群。
