Dunn Katherine L, Zhao Helen, Davie James R
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada.
Exp Cell Res. 2003 Aug 1;288(1):218-23. doi: 10.1016/s0014-4827(03)00185-x.
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.
核DNA被组织成染色质环结构域。在这些环的基部，DNA的基质相关区域（MARs）与核基质蛋白相互作用。MARs在染色质中充当结构边界，并且MAR结合蛋白可能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，顺铂是一种优先使核基质蛋白与DNA原位交联的试剂。这些结果表明CTCF将染色质锚定到核基质上，表明绝缘子与核基质之间存在功能联系。我们还表明，染色质修饰酶HDAC1和HDAC2是固有的核基质成分，被认为是CTCF的共抑制因子，但它们无法与CTCF结合。因此，CTCF的绝缘子活性显然涉及与核基质的不依赖HDAC的结合。我们提出，CTCF可能划定染色质中依赖核基质的转变点，从而形成拓扑独立的染色质环，这可能支持基因沉默。
