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| Status |
Public on Nov 05, 2020 |
| Title |
Brd2/4 and Myc regulate alternative cell lineage programs during early osteoclast development [H3K27ac ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Osteoclast development in response to RANKL is critical for bone homeostasis in health and in disease e.g., osteoporosis and cancer. The early and direct chromatin regulatory changes imparted by BET proteins Brd2-4 and osteoclast-affiliated transcription factors (TF) during osteoclastogenesis are not known. Here we show that as early as 4h post-RANKL, osteoclast development entails regulation of two alternative cell fate transcriptional programs, osteoclast vs. macrophage, with repression of the latter following activation of the former. Pharmacological inhibition shows that this requires increased chromatin binding in a non-redundant manner of Brd2 at promoters and Brd4 at enhancers/super-enhancers. Myc, the top RANKL-induced TF, is predicted to regulate early regulatory events in co-operation with Brd2/4 and Max and by establishing negative and positive regulatory loops with other lineage-affiliated TF. These novel insights into the transcriptional regulation of osteoclastogenesis suggest the clinical potential of selective targeting of Brd2/4 to abrogate aberrant OC activation.
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| Overall design |
Monocyte-derived cell line induced to differentiate to OC by addition of RANKL (50ng/ml). The effect of the BET inhibitor (Ibet-500nM) was studied alone or in combination with RANKL. ChIP-seq was performed in crosslinked cells after 4 hrs.
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| Contributor(s) |
Caputo VS, Trasanidis N, Xiao X, Robinson ME, Katsarou A, Ponnusamy K, Prinjha RK, Smithers N, Chaidos A, Auner HW, Karadimitris A |
| Citation missing |
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| |
| Submission date |
Nov 04, 2020 |
| Last update date |
Nov 07, 2020 |
| Contact name |
Anastasios Karadimitris |
| E-mail(s) |
a.karadimitris@imperial.ac.uk
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| Phone |
+44 20 3313 8438
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| Organization name |
Imperial College London
|
| Department |
Department of Immunology and Inflammation
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| Lab |
Karadimitris' Lab
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| Street address |
Hammersmith Campus, Du Cane Road
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| City |
London |
| ZIP/Postal code |
W12 0NN |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE160840 |
Brd2/4 and Myc regulate alternative cell lineage programs during early osteoclast development |
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| Relations |
| BioProject |
PRJNA674623 |
| SRA |
SRP291153 |
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