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| Status |
Public on Jul 22, 2016 |
| Title |
FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
FOXA1 is a FKHD family protein that translates epigenetic signatures at target enhancers to lineage-specific transcription and differentiation. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of this epigenetic signature, namely DNA hypomethylation and histone 3 lysine 4 methylation. Mechanistically, this involves TET1, a 5-methylcytosine dioxygenase. We found that FOXA1 induces TET1 expression via direct binding at its cis-regulatory elements. Further, FOXA1 physically interacts with the TET1 protein through its CXXC domain. TET1 thus co-occupies FOXA1-dependent enhancers and mediates local DNA demethylation and concomitant histone 3 lysine 4 methylation, further potentiating FOXA1 recruitment. FOXA1 binding events were markedly reduced following TET1 depletion. Together, our results support that FOXA1 is not only a reader, but also a writer, of the epigenetic signatures at lineage-specific enhancers and that TET1 and FOXA1 form a feed-forward regulatory loop for enhancer activation.
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| Overall design |
ChIP-Seq examination of FOXA1 binding sites in LNCaP cell, and epigenetic markers (5mC, 5hmC, H3K4me2) profiling upon TET1 depletion
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| Contributor(s) |
Yu J, Yang YA, Zhao J |
| Citation(s) |
27257062 |
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| Submission date |
Sep 23, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Jindan Yu |
| E-mail(s) |
jindan.yu@emory.edu
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| Organization name |
Emory University
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| Department |
Urology
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| Lab |
Jindan Yu's lab
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| Street address |
E330, 1760 Haygood Dr NE
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
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| Platforms (1) |
| GPL15456 |
Illumina HiScanSQ (Homo sapiens) |
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| Samples (18)
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| GSM1891822 |
PrEC, hMe-Seal-seq |
| GSM1891823 |
LNCaP, hMe-Seal-seq |
| GSM1891824 |
PC-3M, hMe-Seal-seq |
| GSM1891829 |
LNCaP shCtrl, H3K4me2 ChIP-seq |
| GSM1891830 |
LNCaP shCtrl, FOXA1 ChIP-seq |
| GSM1891831 |
LNCaP shTET1, H3K4me2 ChIP-seq |
| GSM1891832 |
LNCaP shTET1, FOXA1 ChIP-seq |
| GSM1891833 |
LNCaP shCtrl, MeDIP-seq |
| GSM1891834 |
LNCaP shTET1, MeDIP-seq |
| GSM1891835 |
LNCaP shCtrl (pLKO), hMe-Seal-seq |
| GSM1891836 |
LNCaP shTET1, hMe-Seal-seq |
| GSM2065592 |
LNCaP shCtrl, MeDIP-seq, rep2 |
| GSM2065593 |
LNCaP shFOXA1, MeDIP-seq |
| GSM2065594 |
LNCaP shCtrl, hMe-Seal-seq |
| GSM2065595 |
LNCaP shFOXA1, hMe-Seal-seq |
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| Relations |
| BioProject |
PRJNA296797 |
| SRA |
SRP064122 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE73363_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of BEDGRAPH, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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