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Brd2/4 and Myc regulate alternative cell lineage programs during early osteoclast development

ABSTRACT: Brd2/4 and Myc regulate alternative cell lineage programs during early osteoclast development

PROVIDER: PRJNA674615 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12980938_1.fastq.gz	Fastqsanger.gz
	SRR12980938_2.fastq.gz	Fastqsanger.gz
	SRR12980939_1.fastq.gz	Fastqsanger.gz
	SRR12980939_2.fastq.gz	Fastqsanger.gz
	SRR12980240_1.fastq.gz	Fastqsanger.gz

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Brd2/4 and Myc regulate alternative cell lineage programs during early osteoclast development [ATAC-seq]

Project description: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.

2020-11-05 | GSE160835 | GEO