Pioneer factors in development and cancer

Benjamin D Sunkel; Benjamin Z Stanton

doi:10.1016/j.isci.2021.103132

Pioneer factors in development and cancer

iScience. 2021 Sep 15;24(10):103132. doi: 10.1016/j.isci.2021.103132. eCollection 2021 Oct 22.

Authors

Benjamin D Sunkel¹, Benjamin Z Stanton^{1

2

3}

Affiliations

¹ Nationwide Children's Hospital, Center for Childhood Cancer and Blood Diseases, Columbus, OH 43205, USA.
² Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43205, USA.
³ Department of Biological Chemistry and Pharmacology, The Ohio State University College of Medicine, Columbus, OH 43210, USA.

Abstract

Transcription factors (TFs) are essential mediators of epigenetic regulation and modifiers of penetrance. Studies from the past decades have revealed a sub-class of TF that is capable of remodeling closed chromatin states through targeting nucleosomal motifs. This pioneer factor (PF) class of chromatin remodeler is ATP independent in its roles in epigenetic initiation, with nucleosome-motif recognition and association with repressive chromatin regions. Increasing evidence suggests that the fundamental properties of PFs can be coopted in human cancers. We explore the role of PFs in the larger context of tissue-specific epigenetic regulation. Moreover, we highlight an emerging class of chimeric PF derived from translocation partners in human disease and PFs associated with rare tumors. In the age of site-directed genome editing and targeted protein degradation, increasing our understanding of PFs will provide access to next-generation therapy for human disease driven from altered transcriptional circuitry.

Keywords: Cancer systems biology; Epigenetics; Molecular biology; Systems biology.

Publication types

Review