title: FOXA1 defines cancer cell specificity.
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.
authors.affiliation: Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Gaihua
authors.identifier: 0000-0003-1038-1049
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Yongbing
authors.identifier: 0000-0002-9917-7425
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Li-Pin
authors.initials: LP
authors.lastname: Kao
authors.affiliation: Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Skerry
authors.affiliation: Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Zhaoyu
authors.identifier: 0000-0002-1136-2758
authors.initials: Z
authors.lastname: Li
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha
keywords: CRISPR; Cell-Specific; FOXA1; breast cancer; liver cancer; prostate cancer