Exchange of GATA factors mediates transitions in looped chromatin organization at a developmentally regulated gene locus
Exchange of GATA factors mediates transitions in looped chromatin organization at a developmentally regulated gene locus
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DOI：
10.1016/j.molcel.2007.11.020
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发表时间：
2008-02-01
期刊：
影响因子：
16
通讯作者：
Blobel, Gerd A.
中科院分区：
文献类型：
--
作者：
Jing, Huie;Vakoc, Christopher R.;Blobel, Gerd A.
增强子可以通过形成染色质环来长距离调节指定启动子。染色质环是否在基因抑制过程中丢失或重新配置，在很大程度上是未知的。我们检查了Kit基因的染色体构象，该基因在早期红细胞生成期间表达，但在细胞成熟后下调。试剂盒表达受两个加塔家族转录因子的顺序占据控制。在未成熟细胞中，由加塔-2结合的远端增强子与活性Kit启动子物理接近。在细胞成熟时，加塔-1置换加塔-2并引发增强子/启动子相互作用的丧失。此外，加塔-1增加了不同下游加塔元件之间在核空间中的接近性。加塔-1诱导的染色质构象转变不仅仅是转录抑制的结果，还需要辅因子FOG-1。这项工作表明，一个加塔因子交换重新配置高阶染色质组织，并建议从头染色质环的形成是由核因子指定的抑制性结果。
Enhancers can regulate designate promoters over long distances by forming chromatin loops. Whether chromatin loops are lost or reconfigured during gene repression is largely unexplored. We examined the chromosome conformation of the Kit gene that is expressed during early erythropoiesis but is downregulated upon cell maturation. Kit expression is controlled by sequential occupancy of two GATA family transcription factors. In immature cells, a distal enhancer bound by GATA-2 is in physical proximity with the active Kit promoter. Upon cell maturation, GATA-1 displaces GATA-2 and triggers a loss of the enhancer/promoter interaction. Moreover, GATA-1 reciprocally increases the proximity in nuclear space among distinct downstream GATA elements. GATA-1-induced transitions in chromatin conformation are not simply the consequence of transcription inhibition and require the cofactor FOG-1. This work shows that a GATA factor exchange reconfigures higher-order chromatin organization, and suggests that de novo chromatin loop formation is employed by nuclear factors to specify repressive outcomes.