FOXA1 defines cancer cell specificity

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

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e1501473
JournalScience advances
Volume2
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • breast cancer
  • Cell-Specific
  • CRISPR
  • FOXA1
  • liver cancer
  • prostate cancer

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Zhang, G., Zhao, Y., Liu, Y., Kao, L. P., Wang, X., Skerry, B., & Li, Z. (2016). FOXA1 defines cancer cell specificity. Science advances, 2(3), e1501473. https://doi.org/10.1126/sciadv.1501473