Histone H3.1 is a chromatin embedded redox sensor triggered by tumor cells developing adaptive phenotypic plasticity and multi-drug resistance [RNA-Seq]

Chromatin structure is regulated through histone post-translational modifications as well as histone variants. Although highly homologous, histone variants display unique amino acid sequences associated with specialized functions in gene transcription regulation. Abnormal incorporation of histone variants into chromatin contributes to cancer initiation, progression, metastasis, as well as, therapy resistance. The current study reports a novel epigenetic function of histone H3.1 as a redox sensor embedded in heterochromatin. We found that this new function depends on oxidation by nuclear ROS and lead to changes in the transcriptional profile of MCF10A cells. Overall design: mRNA was collected from control cells and 4h or 24h after treatment with D-Alanine (ROS generated in the nucleus)

染色质结构的调控依赖于组蛋白翻译后修饰与组蛋白变体。尽管组蛋白变体间同源性极高，但它们拥有独特的氨基酸序列，与基因转录调控中的特异性功能密切相关。组蛋白变体异常嵌入染色质，会促进癌症的发生、进展、转移以及治疗耐药性的产生。本研究揭示了组蛋白H3.1的一种新型表观遗传功能：其作为氧化还原感受器嵌入异染色质中。我们发现，这一新功能依赖于核活性氧（reactive oxygen species, ROS）的氧化作用，并会导致MCF10A细胞的转录谱发生改变。实验整体设计：从对照组细胞以及经D-丙氨酸（可在细胞核内产生活性氧）处理4小时、24小时的细胞中收集mRNA。