lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation.
lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation.
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DOI：
10.1038/s41556-020-0572-2
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发表时间：
2020-10
影响因子：
21.3
通讯作者：
Mullen AC
中科院分区：
文献类型：
--
作者：
Daneshvar K;Ardehali MB;Klein IA;Hsieh FK;Kratkiewicz AJ;Mahpour A;Cancelliere SOL;Zhou C;Cook BM;Li W;Pondick JV;Gupta SK;Moran SP;Young RA;Kingston RE;Mullen AC
DNA、RNA和蛋白质之间的合作通过连接核酸区域和蛋白质结构域的相互作用以及通过生物分子缩合物的组装来调节基因表达并控制分化。在这里，我们报告说，内胚层分化是通过长的非编码（lnc）RNA DIGIT和布罗莫结构域和额外的末端结构域蛋白BRD 3的相互作用进行调节。BRD 3形成相分离的缩合物，其形成由DIGIT促进，占据内胚层转录因子的增强子，并且是内胚层分化所需的。BRD 3在体外结合乙酰化组蛋白H3赖氨酸18（H3 K18 ac），并与H3 K18 ac共占据基因组。DIGIT还在H3 K18 ac的区域中富集，并且DIGIT的耗尽导致BRD 3向这些区域的募集减少。我们的研究结果表明，DIGIT和BRD 3在H3 K18 ac区域之间的合作调节了驱动内胚层分化的转录因子，并表明蛋白质-lncRNA相分离的缩合物作为转录调节因子具有更广泛的作用。
Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions connecting regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated through the interaction of the long noncoding (lnc) RNA DIGIT and the bromodomain and extra-terminal domain protein BRD3. BRD3 forms phase-separated condensates, the formation of which are promoted by DIGIT, occupies enhancers of endoderm transcription factors, and is required for endoderm differentiation. BRD3 binds acetylated histone H3 lysine 18 (H3K18ac) in vitro and co-occupies the genome with H3K18ac. DIGIT is also enriched in regions of H3K18ac, and 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 a broader role for protein-lncRNA phase-separated condensates as regulators of transcription.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B
影响因子：
--
作者：
Abmayr, Susan M;Yao, Tingting;Workman, Jerry L
通讯作者：
Workman, Jerry L
影响因子：
8.8
作者：
Di Micco R;Fontanals-Cirera B;Low V;Ntziachristos P;Yuen SK;Lovell CD;Dolgalev I;Yonekubo Y;Zhang G;Rusinova E;Gerona-Navarro G;Cañamero M;Ohlmeyer M;Aifantis I;Zhou MM;Tsirigos A;Hernando E
通讯作者：
Hernando E
影响因子：
64.5
作者：
Boija A;Klein IA;Sabari BR;Dall'Agnese A;Coffey EL;Zamudio AV;Li CH;Shrinivas K;Manteiga JC;Hannett NM;Abraham BJ;Afeyan LK;Guo YE;Rimel JK;Fant CB;Schuijers J;Lee TI;Taatjes DJ;Young RA
通讯作者：
Young RA