The genome is organized via CTCF–cohesin-binding sites, which partition chromosomes into 1–5 megabase (Mb) topologically associated domains (TADs), and further into smaller sub-domains (sub-TADs). Here we examined in vivo an ~80 kb sub-TAD, containing the mouse α-globin gene cluster, lying within a ~1 Mb TAD. We find that the sub-TAD is flanked by predominantly convergent CTCF–cohesin sites that are ubiquitously bound by CTCF but only interact during erythropoiesis, defining a self-interacting erythroid compartment. Whereas the α-globin regulatory elements normally act solely on promoters downstream of the enhancers, removal of a conserved upstream CTCF–cohesin boundary extends the sub-TAD to adjacent upstream CTCF–cohesin-binding sites. The α-globin enhancers now interact with the flanking chromatin, upregulating expression of genes within this extended sub-TAD. Rather than acting solely as a barrier to chromatin modification, CTCF–cohesin boundaries in this sub-TAD delimit the region of chromatin to which enhancers have access and within which they interact with receptive promoters.

中文翻译：

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组织特异性CTCF-黏着蛋白介导的染色质结构限制了体内增强子的相互作用和功能

基因组是通过CTCF-cohesin结合位点组织的，它将染色体分成1–5 兆碱基（Mb）的拓扑相关域（TAD），再进一步分成较小的子域（sub-TAD）。在这里，我们检查体内的〜80  kb的子TAD，含有小鼠α珠蛋白基因簇，躺在〜1内 MB TAD。我们发现，次TAD的侧翼是主要会聚的CTCF-粘着素位点，这些位点被CTCF无处不在，但仅在红细胞生成过程中相互作用，从而定义了一个自相互作用的类红细胞区室。而α-珠蛋白调节元件通常仅作用于增强子的下游启动子，去除保守的上游CTCF-黏附素边界可将sub-TAD延伸至相邻的上游CTCF-黏附素结合位点。现在，α-珠蛋白增强子与侧染染色质相互作用，从而上调了这个扩展的亚TAD内基因的表达。该亚TAD中的CTCF-粘着蛋白边界并不仅充当染色质修饰的障碍，它还限定了增强剂可进入并与受体启动子相互作用的染色质区域。