染色质的结构高度动态化，这是由于组蛋白和DNA的表观遗传修饰所导致的，这种动态化控制了细胞的可塑性，并允许表观遗传景观的重塑，从而实现细胞分化或细胞（再）编程的要求。为了解表观遗传开关如何实现癌细胞的编程，我们对SH-SY5Y神经母细胞瘤细胞骨生成分化过程中的组蛋白3（H3）修饰进行了全基因组分析。最显著的修饰涉及到H3K27me2/3，H3K9me2，H3K79me1/2和H3K4me1，这些修饰特异性地指定了健康成体干细胞分化过程。接下来，我们在来源于基底细胞瘤、头颈部癌和膀胱肿瘤患者的活检标本中评估了H3K27，H3K9和H3K79的甲基化状态。有趣的是，我们发现癌症标本中H3K9me2和H3K79me3明显减少，与其健康对照组相比，并且这两种表观遗传标志物在所有三种肿瘤中呈正相关。因此，我们认为，H3K9me2和H3K79me3的全局升高，这在正常分化细胞中存在但在恶性肿瘤中丧失，可能反映了肿瘤发生的重要表观遗传屏障。我们的研究进一步通过生物信息学分析揭示了最相关的H3修饰酶的异常表达，从而进一步证实了这一建议。总体而言，我们的研究表明，H3K9me2和H3K79me3的同时发生对于确保分化组织的完整性至关重要，因此它们的综合评估可能是一种新的诊断标志和潜在治疗靶点。

The highly dynamic nature of chromatin's structure, due to the epigenetic alterations of histones and DNA, controls cellular plasticity and allows the rewiring of the epigenetic landscape required for either cell differentiation or cell (re)programming. To dissect the epigenetic switch enabling the programming of a cancer cell, we carried out wide genome analysis of Histone 3 (H3) modifications during osteogenic differentiation of SH-SY5Y neuroblastoma cells. The most significant modifications concerned H3K27me2/3, H3K9me2, H3K79me1/2, and H3K4me1 that specify the process of healthy adult stem cell differentiation. Next, we translated these findings in vivo, assessing H3K27, H3K9, and H3K79 methylation states in biopsies derived from patients affected by basalioma, head and neck carcinoma, and bladder tumors. Interestingly, we found a drastic decrease in H3K9me2 and H3K79me3 in cancer specimens with respect to their healthy counterparts and also a positive correlation between these two epigenetic flags in all three tumors. Therefore, we suggest that elevated global levels of H3K9me2 and H3K79me3, present in normal differentiated cells but lost in malignancy, may reflect an important epigenetic barrier to tumorigenesis. This suggestion is further corroborated, at least in part, by the deranged expression of the most relevant H3 modifier enzymes, as revealed by bioinformatic analysis. Overall, our study indicates that the simultaneous occurrence of H3K9me2 and H3K79me3 is fundamental to ensure the integrity of differentiated tissues and, thus, their combined evaluation may represent a novel diagnostic marker and potential therapeutic target.