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Cancer Cell. 2017 Jul 10;32(1):27-41.e4. doi: 10.1016/j.ccell.2017.05.008. Epub 2017 Jun 15.

Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors.

Author information

1
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.
2
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.
3
Epinomics, Menlo Park, CA 94035, USA.
4
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.
5
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.
6
Stanford Blood and Marrow Transplantation Cellular Therapy Facility, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
7
CNRSUMR 5164, Université de Bordeaux, Bordeaux 33076, France.
8
Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
9
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
10
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 Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
11
Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: younkim@stanford.edu.
12
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. Electronic address: howchang@stanford.edu.

Abstract

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.

KEYWORDS:

CTCL; HDAC inhibitor; cancer epigenetics; response predictor

PMID:
28625481
PMCID:
PMC5559384
DOI:
10.1016/j.ccell.2017.05.008
[Indexed for MEDLINE]
Free PMC Article

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