Nuclear receptor-enhanced transcription requires motor- and LSD1-dependent gene networking in interchromatin granules (Retracted Article. See vol 134, pg 189, 2008)
Nuclear receptor-enhanced transcription requires motor- and LSD1-dependent gene networking in interchromatin granules (Retracted Article. See vol 134, pg 189, 2008)
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DOI：
10.1016/j.cell.2008.01.051
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发表时间：
2008-03-21
期刊：
影响因子：
64.5
通讯作者：
Fu, Xiang-Dong
中科院分区：
文献类型：
--
作者：
Nunez, Esperanza;Kwon, Young-Soo;Fu, Xiang-Dong
虽然转录机制已被广泛解剖在分子水平上，很少有人知道在细胞核的三维空间中的染色体组织的调节，以实现集成的转录反应，以不同的信号事件。在这里，我们报告说，配体诱导雌激素受体α结合的转录单位的子集之间的快速染色体间的相互作用，与一个戏剧性的重组核领土需要核肌动蛋白/肌球蛋白-I运输机械，动力蛋白轻链1（DLC 1），和一个特定的子集的转录辅激活因子和染色质重塑复合物。我们建立了一个要求组蛋白赖氨酸脱甲基酶，LSD 1，在指导特定的染色体间相互作用位点不同的染色质间颗粒，长期以来被认为是“存储”的剪接机器的网站，并证明这些三维电机依赖的相互作用是必需的，以实现增强特定的雌激素受体靶基因的转录。这些发现揭示了哺乳动物细胞核中调控基因表达程序的核结构调节作用。
While the transcriptional machinery has been extensively dissected at the molecular level, little is known about regulation of chromosomal organization in the three-dimensional space of the nucleus to achieve integrated transcriptional responses to diverse signaling events. Here, we report that ligand induces rapid interchromosomal interactions among subsets of estrogen receptor alpha-bound transcription units, with a dramatic reorganization of nuclear territories requiring nuclear actin/myosin-I transport machinery, dynein light chain 1 (DLC1), and a specific subset of transcriptional coactivators and chromatin remodeling complexes. We establish a requirement for the histone lysine demethylase, LSD1, in directing specific interchromosomal interaction loci to distinct interchromatin granules, long thought to be "storage'' sites for splicing machinery, and demonstrate that these three-dimensional motor-dependent interactions are required to achieve enhanced transcription of specific estrogen-receptor target genes. These findings reveal roles for the modulation of nuclear architecture in orchestrating regulated gene-expression programs in the mammalian nucleus.