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GEO help: Mouse over screen elements for information. |
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Status |
Public on May 05, 2017 |
Title |
Mll3 and Mll4 facilitate enhancer RNA synthesis and transcriptional elongation from promoters independently of H3K4 monomethylation |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other
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Summary |
Monomethylation of histone H3 at lysine 4 (H3K4me1) and acetylation of histone H3 at lysine 27 (H3K27ac) are correlated with transcriptionally engaged enhancer elements, but the functional impact of these modifications on enhancer activity is not well understood. Here we used CRISPR/Cas9 genome editing to separate catalytic activity-dependent and independent functions of Mll3 (Kmt2c) and Mll4 (Kmt2d, Mll2), the major enhancer H3K4 monomethyltransferases. Loss of Mll3/4 catalytic activity and H3K4me1 from enhancers causes partial depletion of H3K27ac, but surprisingly minor effects on enhancer Pol II binding, enhancer RNA (eRNA) transcription and gene expression. In contrast, loss of Mll3/4 proteins results in dramatic reduction of eRNA production, concomitant with impaired transcriptional elongation at adjacent promoters. Altogether our results suggest the major coactivator function of Mll3/4 is largely independent of H3K4me1 and instead linked to enhancer Pol II occupancy, eRNA transcription and long-range influence on elongation at target promoters.
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Overall design |
ChIP-seq (Mll3/4, H3K4me1, H3K27ac and Pol II), RNA-seq, Start-seq and ATAC-seq, data from WT, knockout and catalytically-deficient Mll3/4 cell lines.
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Contributor(s) |
Dorighi KM |
Citation(s) |
28483418 |
Submission date |
Apr 21, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Kristel Dorighi |
Organization name |
Stanford University
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Street address |
1291 Welch Rd.
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City |
Stanford |
State/province |
CA |
ZIP/Postal code |
94305 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (48)
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Relations |
BioProject |
PRJNA383847 |
SRA |
SRP104739 |
Supplementary file |
Size |
Download |
File type/resource |
GSE98063_RAW.tar |
8.8 Gb |
(http)(custom) |
TAR (of BW) |
GSE98063_RNAseq_TPMs.csv.gz |
1.7 Mb |
(ftp)(http) |
CSV |
GSE98063_WT-Startseq_F.bedGraph.gz |
3.3 Mb |
(ftp)(http) |
BEDGRAPH |
GSE98063_WT-Startseq_R.bedGraph.gz |
3.2 Mb |
(ftp)(http) |
BEDGRAPH |
GSE98063_dCD-Startseq_F.bedGraph.gz |
1.5 Mb |
(ftp)(http) |
BEDGRAPH |
GSE98063_dCD-Startseq_R.bedGraph.gz |
1.5 Mb |
(ftp)(http) |
BEDGRAPH |
GSE98063_dKO-Startseq_F.bedGraph.gz |
2.4 Mb |
(ftp)(http) |
BEDGRAPH |
GSE98063_dKO-Startseq_R.bedGraph.gz |
2.4 Mb |
(ftp)(http) |
BEDGRAPH |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |
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