Abstract:
Gene expression is regulated by changes in chromatin architecture intrinsic to cellular differentiation and as an active response to environmental stimuli. Chromatin dynamics are a major driver of phenotypic diversity, regulation of development, and manifestation of disease. Remarkably, we know little about the evolutionary dynamics of chromatin reorganisation through time, data essential to characterise the impact of environmental stress during the ongoing biodiversity extinction crisis (20th-21st century). Linking the disparate fields of chromatin biology and museum science through their common use of the preservative formaldehyde (a constituent of formalin), we have generated historical chromatin profiles in museum specimens up to 117 years old. Historical chromatin profiles are reproducible, tissue-specific, sex-specific, and environmental condition-dependent in vertebrate specimens. Additionally, we show that over-fixation modulates differential chromatin accessibility to enable semi-quantitative estimates of relative gene expression in vertebrates and a yeast model. Our approach transforms formalin-fixed biological collections into an accurate, comprehensive, and global record of environmental impact on gene expression and phenotype.
摘要:
基因表达受细胞分化固有的染色质结构变化和对环境刺激的主动反应的调节。染色质动力学是表型多样性的主要驱动因素,发展的调节,和疾病的表现。值得注意的是,我们对染色质重组随时间的进化动力学知之甚少,在持续的生物多样性灭绝危机(20-21世纪)期间,表征环境压力影响所必需的数据。通过共同使用防腐剂甲醛(福尔马林的一种成分),将染色质生物学和博物馆科学的不同领域联系起来,我们已经在博物馆标本中生成了117岁的历史染色质档案。历史染色质谱是可重复的,组织特异性,性别特异性,和环境条件依赖脊椎动物标本。此外,我们表明,过度固定调节差异染色质可及性,从而能够半定量估计脊椎动物和酵母模型中的相对基因表达。我们的方法将福尔马林固定的生物集合转化为准确的,全面,以及全球环境对基因表达和表型的影响记录。