A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions.
A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions.
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DOI：
10.1038/s41467-018-06248-4
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发表时间：
2018-09-21
影响因子：
16.6
通讯作者：
Buckle VJ
中科院分区：
文献类型：
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作者：
Brown JM;Roberts NA;Graham B;Waithe D;Lagerholm C;Telenius JM;De Ornellas S;Oudelaar AM;Scott C;Szczerbal I;Babbs C;Kassouf MT;Hughes JR;Higgs DR;Buckle VJ
自我相互作用的染色质结构域包含基因及其顺式调控元件；然而，结构域采取的三维形式、这是否依赖于增强子-启动子相互作用以及介导此类结构域的形成和维持所需的过程仍不清楚。为了研究这些问题，我们在这里结合使用高分辨率染色体构象捕获、非变性形式的荧光原位杂交和超分辨率成像来研究包含小鼠 α-珠蛋白调节位点的 70 kb 结构域。我们表明，该区域形成了红系特异性的、解压缩的、自相互作用的结构域，在红系终末分化早期由经常并列的 CTCF/粘连蛋白结合位点界定，并且不需要转录延伸来维持结构域结构。该结构域的形成不依赖于 α-珠蛋白基因与其主要增强子之间的相互作用，表明该结构域的建立具有转录无关的机制。然而，主要增强子的缺失确实会改变内部结构域的相互作用。因此，环域的形成似乎是一个机械过程，其发生与内部的特定相互作用无关。自我相互作用的染色质结构域包含基因及其顺式调控元件。在这里，作者使用高分辨率染色体构象捕获和超分辨率成像来研究包含小鼠 α-珠蛋白调节位点的 70 kb 结构域，并发现组织特异性自相互作用染色质结构域的形成独立于增强子-启动子相互作用。
Self-interacting chromatin domains encompass genes and their cis-regulatory elements; however, the three-dimensional form a domain takes, whether this relies on enhancer–promoter interactions, and the processes necessary to mediate the formation and maintenance of such domains, remain unclear. To examine these questions, here we use a combination of high-resolution chromosome conformation capture, a non-denaturing form of fluorescence in situ hybridisation and super-resolution imaging to study a 70 kb domain encompassing the mouse α-globin regulatory locus. We show that this region forms an erythroid-specific, decompacted, self-interacting domain, delimited by frequently apposed CTCF/cohesin binding sites early in terminal erythroid differentiation, and does not require transcriptional elongation for maintenance of the domain structure. Formation of this domain does not rely on interactions between the α-globin genes and their major enhancers, suggesting a transcription-independent mechanism for establishment of the domain. However, absence of the major enhancers does alter internal domain interactions. Formation of a loop domain therefore appears to be a mechanistic process that occurs irrespective of the specific interactions within. Self-interacting chromatin domains encompass genes and their cis-regulatory elements. Here the authors use high-resolution chromosome conformation capture and super-resolution imaging to study a 70 kb domain that includes the mouse α-globin regulatory locus and find that a tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions.
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α-珠蛋白基因结构域的三维折叠揭示了染色质球的形成。
影响因子：
16.8
作者：
通讯作者：
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影响因子：
64.5
作者：
Dowen JM;Fan ZP;Hnisz D;Ren G;Abraham BJ;Zhang LN;Weintraub AS;Schujiers J;Lee TI;Zhao K;Young RA
通讯作者：
Young RA
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：
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
DOI：
10.1126/science.aao3136
发表时间：
2018-03-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu B;Swigut T;Spencley A;Bauer MR;Chung M;Meyer T;Wysocka J
通讯作者：
Wysocka J