尽管转录机器复合物（transcriptional machinery）已经在分子水平上得到了程度的分解，但是目前对于通过调节细胞核中染色体组织的三维空间结构，从而实现各种不同信号的整体转录应答过程尚不清楚。哺乳动物细胞中会发生染色体间相互作用，而伴随着这种相互作用还会产生核结构的显著重组，从而形成“接吻染色体”（kissing chromosomes）。
在2008年3月21日出版的《细胞》（Cell）上，来自美国和意大利的一组科学家证实了雌激素诱导的染色体重组，这种重组对于建立染色体内和染色体间基因网络是必需的，而基因网络则是染色质间颗粒区（interchromatin granule）基因增强表达*的。
文章中描述了配合基诱导的染色体之间快速相互作用，这些相互作用发生在各种雌激素受体α结合转录单位（transcription unit）之间。这种细胞核区域的重构需要核肌动蛋白/肌浆球蛋白（actin/myosin-1）运输机器复合物，细胞动力蛋白轻链1（dynein light chain 1 DLC1），以及一类特殊的转录辅激活物（transcriptional coactivators）和染色质重塑复合物（chromatin remodeling complexes）。在文章中，研究人员提出了组蛋白赖氨酸脱甲基酶（histone lysine demethylase LSD1）对于染色质间颗粒区位点的特定染色体间相互作用是必需的，染色质间颗粒区以来一直被认为是拼接（splicing）机器的储存场所。
除了上述发现之外，科学家们在研究中还证实，这些三维相互作用对于实现特定雌激素受体靶基因的增强转录是必需的。以上研究结果揭示了哺乳动物细胞核基因表达过程中核结构调制所起到的作用。（科学网 何宏辉/编译）（Cell），Vol 132, 996-1010, 21 March 2008，Esperanza Nunez, Xiang-Dong Fu
Nuclear Receptor-Enhanced Transcription Requires Motor- and LSD1-Dependent Gene Networking in Interchromatin Granules
Esperanza Nunez,1,2,7 Young-Soo Kwon,4,7 Kasey R. Hutt,1,5 Qidong Hu,1 Maria Dafne Cardamone,1,6 Kenneth A. Ohgi,1 Ivan Garcia-Bassets,1 David W. Rose,3 Christopher K. Glass,4 Michael G. Rosenfeld,1,Cell细胞核结构调节对基因表达作用 and Xiang-Dong Fu3,Cell细胞核结构调节对基因表达作用Cell细胞核结构调节对基因表达作用
1 Howard Hughes Medical Institute, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA
2 Biomedical Sciences Graduate Program, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA
3 Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA
4 Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA
5 Bioinformatics Graduate Program, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA
6 Department of Oncological Sciences, University of Turin, Turin, Italy
Summary
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 α-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.
