The insulator binding protein CTCF associates with the nuclear matrix
The insulator binding protein CTCF associates with the nuclear matrix
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DOI：
10.1016/s0014-4827(03)00185-x
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发表时间：
2003-08-01
影响因子：
3.7
通讯作者：
Davie, JR
中科院分区：
文献类型：
--
作者：
Dunn, KL;Zhao, H;Davie, JR
核DNA被组织成染色质环结构域。在这些环的底部，DNA的基质相关区域（MARS）与核基质蛋白相互作用。MARS作为染色质内的结构边界，并且MAR结合蛋白可以募集重塑染色质的多蛋白复合物。潜在的肿瘤抑制蛋白CTCF与脊椎动物绝缘子结合，并且是绝缘子活性所必需的。我们证明CTCF与核基质相关，并且可以通过顺铂与DNA交联，顺铂是一种优先将核基质蛋白与DNA原位交联的试剂。这些结果表明，CTCF锚定染色质的核基质，这表明有绝缘体和核基质之间的功能连接。我们还表明，染色质修饰酶HDAC1和HDAC2，这是内在的核基质成分，并认为作为CTCF的辅阻遏物的功能，是不能与CTCF。因此，CTCF的绝缘子活性显然涉及与核基质的HDAC独立关联。我们建议，CTCF可能划定核基质依赖的染色质的过渡点，从而形成拓扑独立的染色质环，可能支持基因沉默。(C)2003 Elsevier Science（美国）。All rights reserved.
Nuclear DNA is organized into chromatin loop domains. At the base of these loops, matrix-associated regions (MARS) of the DNA interact with nuclear matrix proteins. MARS act as structural boundaries within chromatin, and MAR binding proteins may recruit multiprotein complexes that remodel chromatin. The potential tumor suppressor protein CTCF binds to vertebrate insulators and is required for insulator activity. We demonstrate that CTCF is associated with the nuclear matrix and can be cross-linked to DNA by cisplatin, an agent that preferentially cross-links nuclear matrix proteins to DNA in situ. These results suggest that CTCF anchors chromatin to the nuclear matrix, suggesting that there is a functional connection between insulators and the nuclear matrix. We also show that the chromatin-modifying enzymes HDAC1 and HDAC2, which are intrinsic nuclear matrix components and thought to function as corepressors of CTCF, are incapable of associating with CTCF. Hence, the insulator activity of CTCF apparently involves an HDAC-independent association with the nuclear matrix. We propose that CTCF may demarcate nuclear matrix-dependent points of transition in chromatin, thereby forming topologically independent chromatin loops that may support gene silencing. (C) 2003 Elsevier Science (USA). All rights reserved.