Multiscale 3D Genome Rewiring during Mouse Neural Development.
Multiscale 3D Genome Rewiring during Mouse Neural Development.
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DOI：
10.1016/j.cell.2017.09.043
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发表时间：
2017-10-19
期刊：
影响因子：
64.5
通讯作者：
Cavalli G
中科院分区：
文献类型：
--
作者：
Bonev B;Mendelson Cohen N;Szabo Q;Fritsch L;Papadopoulos GL;Lubling Y;Xu X;Lv X;Hugnot JP;Tanay A;Cavalli G
染色体构象捕获技术揭示了基因组折叠的重要见解。然而，空间基因组结构如何与基因表达和细胞命运相关仍不清楚。我们全面绘制了小鼠体外和体内神经分化过程中的3D染色质组织，生成了迄今为止最高分辨率的Hi-C图谱。我们发现，转录与染色质绝缘和长程相互作用相关，但dCas 9介导的激活不足以从头创建边界。此外，我们发现了所有细胞类型中富含外显子的活性基因的基因体之间的长距离接触。在神经分化过程中，活性TADs之间的接触变得不那么明显，而非活性TADs之间的相互作用更强烈。干细胞中广泛的Polycomb网络被破坏，而体内神经转录因子之间的动态相互作用出现。最后，伴随基因表达建立细胞类型特异性增强子-启动子接触。这项工作表明，多种因素影响发育中染色质相互作用的动态。小鼠神经分化过程中的超深Hi-C，体外和体内转录与局部染色质绝缘相关，但不足以使其发生局部染色质绝缘Polycomb网络被破坏，而神经TF位点之间出现新的接触富含外显子的基因体，增强子-启动子，和TF站点小鼠神经分化的C图产生了对影响发育过程中染色质相互作用动态的多种因素的见解。
Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo. Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types. During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact more strongly. An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between neural transcription factors appear in vivo. Finally, cell type-specific enhancer-promoter contacts are established concomitant to gene expression. This work shows that multiple factors influence the dynamics of chromatin interactions in development. Ultra-deep Hi-C during mouse neural differentiation, both in vitro and in vivo Transcription is correlated with, but not sufficient for, local chromatin insulation Polycomb network is disrupted, while novel contacts between neural TF sites appear Dynamic contacts among exon-rich gene bodies, enhancer-promoters, and TF sites An ultrahigh resolution Hi-C map of mouse neural differentiation yields insights into the multiple factors that influence the dynamics of chromatin interactions during development.
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影响因子：
64.8
作者：
Konermann S;Brigham MD;Trevino AE;Joung J;Abudayyeh OO;Barcena C;Hsu PD;Habib N;Gootenberg JS;Nishimasu H;Nureki O;Zhang F
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64.5
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影响因子：
64.5
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Haarhuis JHI;van der Weide RH;Blomen VA;Yáñez-Cuna JO;Amendola M;van Ruiten MS;Krijger PHL;Teunissen H;Medema RH;van Steensel B;Brummelkamp TR;de Wit E;Rowland BD
通讯作者：
Rowland BD
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：
25
作者：
Bibel, M;Richter, J;Barde, YA
通讯作者：
Barde, YA