BRG1 requirement for long-range interaction of a locus control region with a downstream promoter
BRG1 requirement for long-range interaction of a locus control region with a downstream promoter
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DOI：
10.1073/pnas.0806420106
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发表时间：
2009-02-17
影响因子：
11.1
通讯作者：
Bresnick, Emery H.
中科院分区：
文献类型：
--
作者：
Kim, Shin-Il;Bultman, Scott J.;Bresnick, Emery H.
DNA动态包装成染色质是控制多种核过程的基本步骤。虽然某些转录因子和染色体成分促进高阶染色质环的形成，但介导环组装和拆卸的共同调节机制尚不清楚。研究人员利用携带BRG1染色质重塑子半胚等位基因的小鼠，发现BRG1突变破坏了β -珠蛋白基因座控制区和下游β主启动子之间的细胞类型特异性环，尽管这两个位点都有反式作用因子占用。相比之下，不同的环对Brg1突变不敏感。在一个新的基于细胞的系统中，对GATA-1条件等位基因（造血的关键调节因子）的分子分析提供了额外的证据，表明BRG1在染色质结构域激活的早期起作用，介导环。尽管染色质重塑剂诱导核小体结构转变的范例已经建立，但我们的研究结果表明，BRG1在特定染色质环的发生中发挥了重要作用，扩大了其功能的范围。
The dynamic packaging of DNA into chromatin is a fundamental step in the control of diverse nuclear processes. Whereas certain transcription factors and chromosomal components promote the formation of higher-order chromatin loops, the co-regulator machinery mediating loop assembly and disassembly is unknown. Using mice bearing a hypomorphic allele of the BRG1 chromatin remodeler, we demonstrate that the Brg1 mutation abrogated a cell type-specific loop between the beta-globin locus control region and the downstream beta major promoter, despite trans-acting factor occupancy at both sites. By contrast, distinct loops were insensitive to the Brg1 mutation. Molecular analysis with a conditional allele of GATA-1, a key regulator of hematopoiesis, in a novel cell-based system provided additional evidence that BRG1 functions early in chromatin domain activation to mediate looping. Although the paradigm in which chromatin remodelers induce nucleosome structural transitions is well established, our results demonstrating an essential role of BRG1 in the genesis of specific chromatin loops expands the repertoire of their functions.