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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 06, 2016 |
| Title |
FOXA1 directs H3K4 monomethylation at enhancers via recruitment of the methyltransferase MLL3 |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
We performed MLL3 ChIP-seq in breast cancer cells and unexpectedly found that MLL3 binds mostly at non-promoter regions enhancers, in contrast to the prevailing hypothesis. MLL3 was shown to occupy regions marked by FOXA1 occupancy and as expected, H3K4me1 and H3K4me2. MLL3 binding was dependent on FOXA1, indicating that FOXA1 recruits MLL3 to chromatin. Motif analysis and subsequent genomic mapping revealed a role for Grainy head like protein-2 (GRHL2) which was shown to co-occupy regions of the chromatin with MLL3. Regions occupied by all three factors, namely FOXA1, MLL3 and GRHL2, were most enriched in H3K4me1. MLL3 silencing decreased H3K4me1 at enhancer elements, but had no appreciable impact on H3K4me3 at enhancer elements. We identify a complex relationship between FOXA1, MLL3 and H3K4me1 at enhancers in breast cancer and propose a mechanism whereby the pioneer factor FOXA1 can interact with a chromatin modifier MLL3, recruiting it to chromatin to facilitate the deposition of H3K4me1 histone marks, subsequently demarcating active enhancer elements.
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| Overall design |
ChIPseq of MLL3, FOXA1, GRHL2, H3K4me3, H3K4me1 in asynchronous MCF7 cells
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| Contributor(s) |
Jozwik KM, Chernukhin I, Nagarajan S, Serandour AA, Carroll JS |
| Citation(s) |
27926873 |
| Submission date |
May 20, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jason Carroll |
| E-mail(s) |
Jason.Carroll@cruk.cam.ac.uk
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| Phone |
+44 1223 769649
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| Organization name |
Cancer Research UK, Cambridge Institute
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| Street address |
Li Ka Shing Centre, Robinson Way
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| City |
Cambridge |
| ZIP/Postal code |
CB2 ORE |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (37)
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| Relations |
| BioProject |
PRJNA322347 |
| SRA |
SRP075495 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE81714_foxa1_sict-sict_input_peaks.narrowPeak.gz |
1.7 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE81714_foxa1_untreated-mcf7_input_peaks.narrowPeak.gz |
1.2 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE81714_grhl2_untreated-mcf7_input_peaks.narrowPeak.gz |
1.8 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE81714_h3k4me1_sict-sict_input_peaks.broadPeak.gz |
4.0 Mb |
(ftp)(http) |
BROADPEAK |
| GSE81714_h3k4me1_simll3-sict_input_peaks.broadPeak.gz |
4.2 Mb |
(ftp)(http) |
BROADPEAK |
| GSE81714_h3k4me3_sict-sict_input_peaks.broadPeak.gz |
988.3 Kb |
(ftp)(http) |
BROADPEAK |
| GSE81714_h3k4me3_simll3-sict_input_peaks.broadPeak.gz |
855.1 Kb |
(ftp)(http) |
BROADPEAK |
| GSE81714_mll3_sict-sict_input_peaks.narrowPeak.gz |
1.2 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE81714_mll3_sifoxa1-sict_input_peaks.narrowPeak.gz |
855.4 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE81714_mll3_untreated-sict_input_peaks.narrowPeak.gz |
488.7 Kb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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