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 language | English (US) |
|---|---|
| Pages (from-to) | e1501473 |
| Journal | Science advances |
| Volume | 2 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2016 |
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Keywords
- breast cancer
- Cell-Specific
- CRISPR
- FOXA1
- liver cancer
- prostate cancer
ASJC Scopus subject areas
- Medicine(all)
Cite this
FOXA1 defines cancer cell specificity. / Zhang, Gaihua; Zhao, Yongbing; Liu, Yi; Kao, Li Pin; Wang, Xiao; Skerry, Benjamin; Li, Zhaoyu.
In: Science advances, Vol. 2, No. 3, 01.03.2016, p. e1501473.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - FOXA1 defines cancer cell specificity
AU - Zhang, Gaihua
AU - Zhao, Yongbing
AU - Liu, Yi
AU - Kao, Li Pin
AU - Wang, Xiao
AU - Skerry, Benjamin
AU - Li, Zhaoyu
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - breast cancer
KW - Cell-Specific
KW - CRISPR
KW - FOXA1
KW - liver cancer
KW - prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85010070551&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85010070551&partnerID=8YFLogxK
U2 - 10.1126/sciadv.1501473
DO - 10.1126/sciadv.1501473
M3 - Article
C2 - 27034986
AN - SCOPUS:85010070551
VL - 2
SP - e1501473
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 3
ER -