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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2017 Jun 20

PMID 28625481

Citations 87

Authors

Kun Qu

Lisa C Zaba

Ansuman T Satpathy

Paul G Giresi

Rui Li

Yonghao Jin

Randall Armstrong

Chen Jin

Nathalie Schmitt

Ziba Rahbar

Hideki Ueno

William J Greenleaf

Youn H Kim

Howard Y Chang

Affiliations

Soon will be listed here.

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.

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