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Publication : lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation.

First Author  Daneshvar K Year  2020
Journal  Nat Cell Biol Volume  22
Issue  10 Pages  1211-1222
PubMed ID  32895492 Mgi Jnum  J:343121
Mgi Id  MGI:6709624 Doi  10.1038/s41556-020-0572-2
Citation  Daneshvar K, et al. (2020) lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation. Nat Cell Biol 22(10):1211-1222
abstractText  Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein BRD3. BRD3 forms phase-separated condensates of which the formation is promoted by DIGIT, occupies enhancers of endoderm transcription factors and is required for endoderm differentiation. BRD3 binds to histone H3 acetylated at lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and the depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings show that cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest that protein-lncRNA phase-separated condensates have a broader role as regulators of transcription.
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