Enhancer dysfunction in leukemia

Bhagwat, A. S., Lu, B., Vakoc, C. R. (April 2018) Enhancer dysfunction in leukemia. Blood, 131 (16). pp. 1795-1804. ISSN 0006-4971

URL: https://www.ncbi.nlm.nih.gov/pubmed/29439951
DOI: 10.1182/blood-2017-11-737379

Abstract

Hematopoietic cancers are often initiated by deregulation of the transcriptional machinery. Prominent among such regulators are the sequence-specific DNA-binding transcription factors (TFs), which bind to enhancer and promoter elements in the genome to control gene expression through the recruitment of cofactors. Remarkably, perturbing the function of even a single TF or cofactor can modulate the active enhancer landscape of a cell and, conversely, knowledge of the enhancer configuration can be used to discover functionally important TFs in a given cellular process. Our expanding insight into enhancer function can be attributed to the emergence of genome-scale measurements of enhancer activity, which can be applied to virtually any cell type to expose regulatory mechanisms. Such approaches are beginning to reveal the abnormal enhancer configurations present in cancer cells, thereby providing a framework for understanding how transcriptional dysregulation can lead to malignancy. Here, we review the evidence for alterations in enhancer landscapes contributing to the pathogenesis of leukemia, a malignancy in which enhancer-binding proteins and enhancer DNA itself are altered via genetic mutation. We will also highlight examples of small-molecules that reprogram the enhancer landscape of leukemia cells in association with therapeutic benefit.

Item Type: Paper
Subjects: diseases & disorders > cancer > cancer types > leukemia
CSHL Authors:
Communities: CSHL labs > Vakoc lab
CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
Depositing User: Matt Covey
Date: 19 April 2018
Date Deposited: 21 Feb 2018 15:00
Last Modified: 12 Jun 2018 18:59
PMCID: PMC5909760
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36074

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