Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules
Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules
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DOI：
10.1073/pnas.0810634105
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发表时间：
2008-12-09
影响因子：
11.1
通讯作者：
Fu, Xiang-Dong
中科院分区：
文献类型：
--
作者：
Hu, Qidong;Kwon, Young-Soo;Fu, Xiang-Dong
虽然配体核受体在介导辅激活子/辅阻遏子交换中的作用是公认的，但对于在核的三维空间中染色体组织在实现对不同信号事件的整合转录响应中的潜在调节知之甚少。在这里，我们报告说，配体诱导快速染色体间的相互作用之间的特定子集的雌激素受体α结合的转录单位，与一个显着的重组核领土，这取决于核肌动蛋白/肌球蛋白-I机械和动力蛋白轻链1的行动。这些配体诱导的相互作用位点需要组蛋白赖氨酸脱甲基酶LSD 1与不同的染色质间颗粒相关联，长期以来，染色质间颗粒被认为是剪接机制、一些关键转录延伸因子和各种染色质重塑复合物的“储存”位点。我们证明，这2步核重排是实现增强，协调转录的核受体靶基因的必要条件。
Although the role of liganded nuclear receptors in mediating coactivator/corepressor exchange is well-established, little is known about the potential regulation of chromosomal organization in the 3-dimensional space of the nucleus in achieving integrated transcriptional responses to diverse signaling events. Here, we report that ligand induces rapid interchromosomal interactions among specific subsets of estrogen receptor alpha-bound transcription units, with a dramatic reorganization of nuclear territories, which depends on the actions of nuclear actin/myosin-I machinery and dynein light chain 1. The histone lysine demethylase, LSD1, is required for these ligand-induced interactive loci to associate with distinct interchromatin granules, long thought to serve as "storage'' sites for the splicing machinery, some critical transcription elongation factors, and various chromatin remodeling complexes. We demonstrate that this 2-step nuclear rearrangement is essential for achieving enhanced, coordinated transcription of nuclear receptor target genes.