盡管轉(zhuǎn)錄機(jī)器復(fù)合物（transcriptional machinery）已經(jīng)在分子水平上得到了程度的分解，但是目前對(duì)于通過調(diào)節(jié)細(xì)胞核中染色體組織的三維空間結(jié)構(gòu)，從而實(shí)現(xiàn)各種不同信號(hào)的整體轉(zhuǎn)錄應(yīng)答過程尚不清楚。哺乳動(dòng)物細(xì)胞中會(huì)發(fā)生染色體間相互作用，而伴隨著這種相互作用還會(huì)產(chǎn)生核結(jié)構(gòu)的顯著重組，從而形成“接吻染色體”（kissing chromosomes）。
在2008年3月21日出版的《細(xì)胞》（Cell）上，來自美國和意大利的一組科學(xué)家證實(shí)了雌激素誘導(dǎo)的染色體重組，這種重組對(duì)于建立染色體內(nèi)和染色體間基因網(wǎng)絡(luò)是必需的，而基因網(wǎng)絡(luò)則是染色質(zhì)間顆粒區(qū)（interchromatin granule）基因增強(qiáng)表達(dá)*的。
文章中描述了配合基誘導(dǎo)的染色體之間快速相互作用，這些相互作用發(fā)生在各種雌激素受體α結(jié)合轉(zhuǎn)錄單位（transcription unit）之間。這種細(xì)胞核區(qū)域的重構(gòu)需要核肌動(dòng)蛋白/肌漿球蛋白（actin/myosin-1）運(yùn)輸機(jī)器復(fù)合物，細(xì)胞動(dòng)力蛋白輕鏈1（dynein light chain 1 DLC1），以及一類特殊的轉(zhuǎn)錄輔激活物（transcriptional coactivators）和染色質(zhì)重塑復(fù)合物（chromatin remodeling complexes）。在文章中，研究人員提出了組蛋白賴氨酸脫甲基酶（histone lysine demethylase LSD1）對(duì)于染色質(zhì)間顆粒區(qū)位點(diǎn)的特定染色體間相互作用是必需的，染色質(zhì)間顆粒區(qū)以來一直被認(rèn)為是拼接（splicing）機(jī)器的儲(chǔ)存場(chǎng)所。
除了上述發(fā)現(xiàn)之外，科學(xué)家們?cè)谘芯恐羞€證實(shí)，這些三維相互作用對(duì)于實(shí)現(xiàn)特定雌激素受體靶基因的增強(qiáng)轉(zhuǎn)錄是必需的。以上研究結(jié)果揭示了哺乳動(dòng)物細(xì)胞核基因表達(dá)過程中核結(jié)構(gòu)調(diào)制所起到的作用。（科學(xué)網(wǎng) 何宏輝/編譯）（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細(xì)胞核結(jié)構(gòu)調(diào)節(jié)對(duì)基因表達(dá)作用 and Xiang-Dong Fu3,Cell細(xì)胞核結(jié)構(gòu)調(diào)節(jié)對(duì)基因表達(dá)作用Cell細(xì)胞核結(jié)構(gòu)調(diào)節(jié)對(duì)基因表達(dá)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.