FOXA1 defines cancer cell specificity

A transcription factor functions differentially and/or identically in multiple cell types. However, the mechanism for cell-specific regulation of a transcription factor remains to be elucidated. We address how a single transcription factor, forkhead box protein A1 (FOXA1), forms cell-specific genomic signatures and differentially regulates gene expression in four human cancer cell lines (HepG2, LNCaP, MCF7, and T47D).

FOXA1 is a pioneer transcription factor in organogenesis and cancer progression. Genomewide mapping of FOXA1 by chromatin immunoprecipitation sequencing annotates that target genes associated with FOXA1 binding are mostly common to these cancer cells. However, most of the functional FOXA1 target genes are specific to each cancer cell type. Further investigations using CRISPR-Cas9 genome editing technology indicate that cell-specific FOXA1 regulation is attributable to unique FOXA1 binding, genetic variations, and/or potential epigenetic regulation. Thus, FOXA1 controls the specificity of cancer cell types. We raise a "flower-blooming" hypothesis for cell-specific transcriptional regulation based on these observations.

Science advances. 2016 Mar 18*** epublish ***

Gaihua Zhang, Yongbing Zhao, Yi Liu, Li-Pin Kao, Xiao Wang, Benjamin Skerry, Zhaoyu Li

Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA., Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA., Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA., Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA., Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA., Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA., Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.

E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe