CTCF-binding sites within the H19 ICR differentially regulate local chromatin structures and cis-acting functions
CTCF-binding sites within the H19 ICR differentially regulate local chromatin structures and cis-acting functions
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H19 ICR 内的 CTCF 结合位点差异调节局部染色质结构和顺式作用功能
DOI：
10.4161/epi.19487
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发表时间：
2012-04-01
期刊：
影响因子：
3.7
通讯作者：
Ohlsson, Rolf
中科院分区：
文献类型：
--
作者：
Guibert, Sylvain;Zhao, Zhihu;Ohlsson, Rolf
通常认为，CTCF结合位点通过促进染色质环的形成而等同于表达结构域的划分。然而，我们早些时候已经提出，这些功能可能依赖于上下文。为了支持这一概念，我们在这里表明，在H19印记控制区(ICR)的母系等位基因内，分别在5‘端和3’端的CTCF结合位点1/2和3/4上的染色质环结构有显著不同。虽然取消CTCF与母体H19ICR等位基因的结合会导致3‘-区染色质环的丢失，但影响5’-区的长距离染色质环显著增加。由于其四个CTCF结合位点的占据程度不同于染色质绝缘体和复制计时功能，我们认为H19 ICR内的CTCF结合位点在功能上是多样化的，并组织了上下文相关的高阶染色质构象。
It is generally assumed that CTCF-binding sites are synonymous with the demarcation of expression domains by promoting the formation of chromatin loops. We have proposed earlier, however, that such features may be context-dependent. In support of this notion, we show here that chromatin loop structures, impinging on CTCF-binding sites 1/2 and 3/4 at the 5′ and 3′-ends, respectively, within the maternal allele of the H19 imprinting control region (ICR), differ significantly. Although abrogation of CTCF binding to the maternal H19 ICR allele results in loss of chromatin loops in the 3′-region, there is a dramatic gain of long-range chromatin loops impinging on the 5′-region. As the degree of occupancy of its four CTCF-binding sites discriminates between the chromatin insulator and replication timing functions, we submit that the CTCF-binding sites within the H19 ICR are functionally diverse and organize context-dependent higher order chromatin conformations.