LncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation [RIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE149032 | GEO | 2020/07/08
REPOSITORIES: GEO
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Project description:Gene programs that control differentiation are regulated through the interplay between DNA, RNA, and protein. Cooperation among these fundamental cellular components can occur through highly structured interactions connecting domains formed by specific sequences of nucleotides, ribonucleotides, and/or amino acids and also through the assembly of biomolecular condensates. Here, we show that endoderm differentiation is regulated through the interaction of the long noncoding (lnc) RNA DIGITand the bromodomain and extra-terminal (BET) domain family protein BRD3. BRD3 forms phase-separated condensates that contain DIGIT, occupies enhancers of endoderm transcription factors, and is required for endoderm differentiation. Purified BRD3 binds to acetylated histone H3 lysine 18 (H3K18ac) in vitro and occupies regions of the genome enriched in H3K18ac during endoderm differentiation, including the key transcription factors that regulate endoderm differentiation. DIGIT is also enriched in regions of H3K18ac, and depletion of DIGIT results in decreased recruitment of BRD3 to these regions. Our findings support a model where cooperation between DIGIT and BRD3 at regions of H3K18ac regulates the transcription factors that drive endoderm differentiation and suggest a broader role for protein-lncRNA phase-separated condensates as regulators of transcription in development.
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Project description:lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation
| PRJNA522865 | ENA
Project description:lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation [RIP-seq]
| PRJNA627192 | ENA
Project description: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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Project description:Endoderm differentiation is a critical step leading to development of the gastrointestinal system. We found that DIGIT is a lncRNA that is required for endoderm differentiation. We used directional RNA sequencing (RNA-seq) to globally evaluate the effects of loss of DIGIT expression during endoderm differentiation and chromatin immunoprecipitation and sequencing (ChIP-seq) to define the sites occupied by SMAD3 during endoderm diferentiation.
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Project description:As the only truly flying mammals, bats use their unique wing formed from elongated digits connected by membranes to power their flight. The forelimb of bats consists of four elongated digits (digits II-V) and one shorter digit (digit I) that is morphologically similar to the hindlimb digits. Elongation of bat forelimb digits is thought to results from changes in the temporal and spatial expression of a number of developmental genes. As a result, comparing gene expression profiles between short and elongated digit morphologies of the fore- and hindlimbs may elucidate the molecular mechanisms underlying digit elongation in bats. Here, we performed a large-scale analysis of gene expression of forelimb digit I, forelimb digits II-V, and all five hindlimb digits in Myotis ricketti using digital gene expression tag profiling approach. Results of this study not only implicate several developmental genes as robust candidates underlying digit elongation in bats, but also provide a better understanding of the genes involved in autopodial development in general.
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