Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors.
Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors.
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DOI：
10.1016/j.ccell.2017.05.008
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发表时间：
2017-07-10
期刊：
影响因子：
50.3
通讯作者：
Chang HY
中科院分区：
文献类型：
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作者：
Qu K;Zaba LC;Satpathy AT;Giresi PG;Li R;Jin Y;Armstrong R;Jin C;Schmitt N;Rahbar Z;Ueno H;Greenleaf WJ;Kim YH;Chang HY
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的景观和动态。对111例人CTCL和对照样本的分析揭示了广泛的染色质特征，这些特征区分了白血病、宿主和正常CD 4 + T细胞。我们确定了三种主要的转录因子（TF）激活模式，驱动白血病调节组，以及TF失活，改变CTCL患者的宿主T细胞。对组蛋白去乙酰化酶抑制剂（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CD 4 + T细胞中引起不同的染色质反应，将宿主T细胞重编程至正常状态。这些结果为研究人类癌症和表观遗传治疗中的个人调节组提供了基础框架。Qu等人表明，可接近的染色质景观将皮肤T细胞淋巴瘤（CTCL）患者中的白血病T细胞与宿主T细胞以及来自健康个体的T细胞区分开。CTCL对HDAC抑制剂的临床反应与染色质可及性的同时获得密切相关。
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. Qu et al. show that the accessible chromatin landscape distinguishes leukemic from host T cells in cutaneous T cell lymphoma (CTCL) patients as well as T cells from healthy individuals. The clinical response of CTCL to HDAC inhibitors strongly associates with a concurrent gain in chromatin accessibility.
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选择性抑制BET溴结构域。
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