Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding.
Resolving the 3D Landscape of Transcription-Linked Mammalian Chromatin Folding.
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DOI：
10.1016/j.molcel.2020.03.002
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发表时间：
2020-05-07
期刊：
影响因子：
16
通讯作者：
Darzacq X
中科院分区：
文献类型：
--
作者：
Hsieh TS;Cattoglio C;Slobodyanyuk E;Hansen AS;Rando OJ;Tjian R;Darzacq X
虽然在大规模的表观基因组区室和拓扑相关结构域的基因组折叠现在相对较好地理解，染色质如何折叠在更精细的尺度仍然在很大程度上未探索的哺乳动物。在这里，我们通过使用高分辨率Micro-C来探测小鼠干细胞中3D基因组组织与转录调控之间的联系，克服了传统基于3C的方法的一些局限性。转录因子、辅因子和染色质修饰剂的组合结合在空间上将多梳区域分离成具有不同调控特征的各种更精细尺度的结构，包括连接启动子与启动子（P-P）或增强子与启动子（E-P）的条带、点和结构域，以及Polycomb区域之间的束接触。从结构域的边缘延伸的E-P条带主要连接共表达的基因座，通常在CTCF和粘附素占据的情况下。转录的急性抑制破坏了这些基因相关的折叠功能，而不改变高阶染色质结构。我们的研究揭示了以前模糊的精细尺度基因组组织，建立染色质折叠和基因调控之间的功能联系。Hsieh等人描述了使用Micro-C（一种增强的染色体构象捕获方法）在哺乳动物细胞中以单核小体分辨率进行的染色质折叠。Micro-C揭示了由基因活性、转录调控和基因沉默形成的全基因组、精细尺度的染色质组织特征。
Whereas folding of genomes at the large scale of epigenomic compartments and topologically associating domains is now relatively well understood, how chromatin is folded at finer scales remains largely unexplored in mammals. Here, we overcome some limitations of conventional 3C-based methods by using high-resolution Micro-C to probe links between 3D genome organization and transcriptional regulation in mouse stem cells. Combinatorial binding of transcription factors, cofactors, and chromatin modifiers spatially segregates TAD regions into various finer-scale structures with distinct regulatory features including stripes, dots, and domains linking promoters-to-promoters (P-P) or enhancers-to-promoters (E-P), and bundle contacts between Polycomb regions. E-P stripes extending from the edge of domains predominantly link co-expressed loci, often in the absence of CTCF and cohesin occupancy. Acute inhibition of transcription disrupts these gene-related folding features without altering higher-order chromatin structures. Our study uncovers previously obscured finer-scale genome organization, establishing functional links between chromatin folding and gene regulation. Hsieh et al. describe chromatin folding at single-nucleosome resolution in mammalian cells using Micro-C, an enhanced chromosome conformation capture method. Micro-C uncovers genome-wide, fine-scale chromatin organizational features shaped by gene activity, transcriptional regulation, and gene silencing.
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DOI：
10.1038/nrg3454
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
7
作者：
Beagan JA;Duong MT;Titus KR;Zhou L;Cao Z;Ma J;Lachanski CV;Gillis DR;Phillips-Cremins JE
通讯作者：
Phillips-Cremins JE
影响因子：
9.3
作者：
Durand NC;Shamim MS;Machol I;Rao SS;Huntley MH;Lander ES;Aiden EL
通讯作者：
Aiden EL
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
64.5
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
通讯作者：
Cavalli G