Qu Kun, Zaba Lisa C, Satpathy Ansuman T, Giresi Paul G, Li Rui, Jin Yonghao, Armstrong Randall, Jin Chen, Schmitt Nathalie, Rahbar Ziba, Ueno Hideki, Greenleaf William J, Kim Youn H, Chang Howard Y
CAS Key Laboratory of Innate Immunity and Chronic Diseases, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China; Center for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine, CCSR 2155c, 269 Campus Drive, Stanford, CA 94305-5168, USA.
Center for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine, CCSR 2155c, 269 Campus Drive, Stanford, CA 94305-5168, USA; Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cancer Cell. 2017 Jul 10;32(1):27-41.e4. doi: 10.1016/j.ccell.2017.05.008. Epub 2017 Jun 15.
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.
在此，我们通过ATAC测序定义了皮肤T细胞淋巴瘤（CTCL）中活性调控DNA的格局和动态变化。对111份人类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CD4 T细胞。我们确定了驱动白血病调控组的三种主要转录因子（TF）激活模式，以及改变CTCL患者宿主T细胞的TF失活模式。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增加密切相关。HDACi在白血病和宿主CD4 T细胞中引起不同的染色质反应，使宿主T细胞重编程恢复正常。这些结果为研究人类癌症中的个人调控组和表观遗传治疗提供了一个基础框架。
