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| Status |
Public on Jan 19, 2023 |
| Title |
The impact of SWI/SNF and NuRD inactivation on gene expression is tightly coupled with levels of RNA Polymerase II occupancy at promoters |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
SWI/SNF and NuRD are protein complexes that antagonistically regulate DNA accessibility. However, repression of their activities often leads to unanticipated changes in target gene expression (paradoxical), highlighting our incomplete understanding of their activities. Here we show that SWI/SNF and NuRD are in a tug-of-war to regulate PRC2 occupancy at lowly expressed and bivalent genes in mESCs. In contrast, at promoters of average or highly expressed genes, SWI/SNF and NuRD antagonistically modulate RNA Polymerase II release kinetics, arguably via modifying H3.3 and H2A.Z turnover rates at promoter-flanking nucleosomes, leading to paradoxical changes in gene expression. Owing to this mechanism, the relative activities of the two remodelers potentiate gene promoters towards Pol II-dependent open or PRC2-dependent closed chromatin states. Our results highlight RNA Polymerase II occupancy as the primary parameter determining the direction of gene expression changes in response to SWI/SNF and NuRD inactivation at gene promoters in mESCs.
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| Overall design |
ChIP-seq (Spike-in) of RNA Polymerase II, H2A.Z and H3.3 in WT ESC and ESCs treated with BRG1 inhibitor or CHD4 shRNA. RNA Polymerase II ChIP-seq were performed in biological triplicates. H2A.Z and H3.3 ChIP-seq were performed in biological duplicates.
Nascent RNA-Seq from mESC treated with BRG1 inhibitor (BRM014) or DMSO (control) and from mESC treated with Chd4 shRNA KD or scramble shRNA (control). RNA samples were spiked in with external reference RNA (synthetic ERCC RNA) based on cell number for sequencing read normalization. There are biological duplicates for each condition
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| Contributor(s) |
Pundhir S, Su J, Tapia M, Hansen AM, Haile JS, Hansen K, Porse BT |
| Citation(s) |
36927987 |
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| Submission date |
Jun 20, 2022 |
| Last update date |
Apr 12, 2023 |
| Contact name |
Bo Porse |
| Organization name |
University of Copenhagen
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| Department |
Finsen Laboratory and BRIC
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| Lab |
Porse lab
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| Street address |
Ole Maaløes Vej 5, 4
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| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (48)
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| GSM6255441 |
Pol II (ser-5p) (BRM014, Rep1) |
| GSM6255442 |
Pol II (ser-5p) (BRM014, Rep2) |
| GSM6255443 |
Pol II (ser-5p) (BRM014, Rep3) |
| GSM6255444 |
Pol II (ser-2p) (Brg1 WT, Rep1) |
| GSM6255445 |
Pol II (ser-2p) (Brg1 WT, Rep2) |
| GSM6255446 |
Pol II (ser-2p) (Brg1 WT, Rep3) |
| GSM6255447 |
Pol II (ser-2p) (BRM014, Rep1) |
| GSM6255448 |
Pol II (ser-2p) (BRM014, Rep2) |
| GSM6255449 |
Pol II (ser-2p) (BRM014, Rep3) |
| GSM6255450 |
Pol II (ser-5p) (Chd4 WT, Rep1) |
| GSM6255451 |
Pol II (ser-5p) (Chd4 WT, Rep2) |
| GSM6255452 |
Pol II (ser-5p) (Chd4 WT, Rep3) |
| GSM6255453 |
Pol II (ser-5p) (Chd4 shRNA, Rep1) |
| GSM6255454 |
Pol II (ser-5p) (Chd4 shRNA, Rep2) |
| GSM6255455 |
Pol II (ser-5p) (Chd4 shRNA, Rep3) |
| GSM6255456 |
Pol II (ser-2p) (Chd4 WT, Rep1) |
| GSM6255457 |
Pol II (ser-2p) (Chd4 WT, Rep2) |
| GSM6255458 |
Pol II (ser-2p) (Chd4 WT, Rep3) |
| GSM6255459 |
Pol II (ser-2p) (Chd4 shRNA, Rep1) |
| GSM6255460 |
Pol II (ser-2p) (Chd4 shRNA, Rep2) |
| GSM6255461 |
Pol II (ser-2p) (Chd4 shRNA, Rep3) |
| GSM6255462 |
H2A.Z (Brg1 WT, Rep1) |
| GSM6255463 |
H2A.Z (Brg1 WT, Rep2) |
| GSM6255464 |
H2A.Z (BRM014, Rep1) |
| GSM6255465 |
H2A.Z (BRM014, Rep2) |
| GSM6255466 |
H3.3 (Brg1 WT, Rep1) |
| GSM6255467 |
H3.3 (Brg1 WT, Rep2) |
| GSM6255468 |
H3.3 (BRM014, Rep1) |
| GSM6255469 |
H3.3 (BRM014, Rep2) |
| GSM6255470 |
H2A.Z (Chd4 WT, Rep1) |
| GSM6255471 |
H2A.Z (Chd4 WT, Rep2) |
| GSM6255472 |
H2A.Z (Chd4 shRNA, Rep1) |
| GSM6255473 |
H2A.Z (Chd4 shRNA, Rep2) |
| GSM6255474 |
H3.3 (Chd4 WT, Rep1) |
| GSM6255475 |
H3.3 (Chd4 WT, Rep2) |
| GSM6255476 |
H3.3 (Chd4 shRNA, Rep1) |
| GSM6255477 |
H3.3 (Chd4 shRNA, Rep2) |
| GSM6784622 |
BRM014_Rep1 |
| GSM6784623 |
BRM014_Rep2 |
| GSM6784624 |
Chd4_shRNA_Rep1 |
| GSM6784625 |
Chd4_shRNA_Rep2 |
| GSM6784626 |
DMSO_Rep1 |
| GSM6784627 |
DMSO_Rep2 |
| GSM6784628 |
SCR_shRNA_Rep1 |
| GSM6784629 |
SCR_shRNA_Rep2 |
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| Relations |
| BioProject |
PRJNA851078 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE206497_GENE_EXPRESSION.MATRIX.ercc.txt.gz |
1.0 Kb |
(ftp)(http) |
TXT |
| GSE206497_GENE_EXPRESSION.MATRIX.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE206497_RAW.tar |
4.9 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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