Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4+T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4+T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy.

中文翻译：

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皮肤T细胞淋巴瘤的染色质可及性景观和对HDAC抑制剂的动态响应

在这里，我们通过ATAC-seq定义了皮肤T细胞淋巴瘤（CTCL）中活性调控DNA的态势和动力学。对111个人CTCL和对照样品的分析显示，广泛的染色质特征可区分白血病，宿主和正常CD4 + T细胞。我们确定三种主要模式的转录因子（TF）激活驱动白血病调节，以及TF失活改变CTCL患者的宿主T细胞。对组蛋白脱乙酰基酶抑制剂（HDACi）的临床反应与染色质可及性的同时获得密切相关。HDACi在白血病和宿主CD4 + T细胞中引起明显的染色质反应，从而将宿主T细胞重新编程为正常状态。这些结果为研究人类癌症和表观遗传学治疗中的个人规律提供了基础框架。