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| Status |
Public on Aug 06, 2019 |
| Title |
Interplay between FACT subunit SPT16 and TRIM33 can remodel chromatin at macrophage distal regulatory elements [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Although the advances in genome-wide approaches have elucidated the functions of macrophage-specific distal regulatory elements in transcriptional responses, chromatin structures associated with PU.1 priming and the underlying mechanisms of action of these cis-acting sequences are not characterized.
Here, we show that, in macrophages, FACT subunit SPT16 can bind to positioned nucleosomes directly flanking PU.1-bound sites at previously uncharacterized distal regulatory elements located near genes essential for macrophage development and functions. SPT16 can interact with the transcriptional co-regulator TRIM33 and binds to half of these sites in a TRIM33 dependent manner. Using the Atp1b3 locus as a model, we show that FACT binds to two positioned nucleosomes surrounding a TRIM33/PU.1-bound site in a region, located 35kb upstream the Atp1b3 TSS, that interact with the Atp1b3 promoter. At this -35kb region, TRIM33 deficiency leads to FACT release, loss of the two positioned nucleosomes, RNA Pol II recruitment and bidirectional transcription. These modifications are associated with higher levels of FACT binding at the Atp1b3 promoter, an increase of RNA Pol II recruitment and an increased expression of Atp1b3 in Trim33-/- macrophages.
Thus, sequestering of SPT16/FACT by TRIM33 at PU.1-bound distal regions might represent a new regulatory mechanism for RNA Pol II recruitment and transcription output in macrophages.
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| Overall design |
ATAC-seq of wild-type and Trim33-/- bone marrow-derived macrophages (BMDM).
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| Contributor(s) |
Ferri F, Romeo PH |
| Citation(s) |
31331374 |
| Submission date |
Jun 18, 2019 |
| Last update date |
Aug 06, 2019 |
| Contact name |
federica ferri |
| E-mail(s) |
federica.ferri@cea.fr
|
| Organization name |
cea
|
| Street address |
18 route du panorama
|
| City |
Fontenay aux roses |
| ZIP/Postal code |
92265 |
| Country |
France |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE132924 |
Interplay between FACT subunit SPT16 and TRIM33 can remodel chromatin at macrophage distal regulatory elements |
|
| Relations |
| BioProject |
PRJNA549476 |
| SRA |
SRP201767 |
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