在雌性哺乳動物中，被稱為XIST的大非編碼RNA觸發(fā)兩個X-染色體中其中一個上的基因轉(zhuǎn)錄被沉默,。X-染色體的這種失活是重要的,，因為雙倍劑量的X基因?qū)⑹怯泻Φ?。在這項研究中,，Jeanne Lawrence及同事用“鋅指核酸酶”來將一個可誘導的XIST轉(zhuǎn)基因定位到來自“唐氏綜合癥”多能干細胞的21號染色體中（這種病是由第三個21號染色體的存在造成的）。他們發(fā)現(xiàn),，XIST RNA覆蓋一個版本的21號染色體,，并觸發(fā)基因沉默，這說明了該方法對于研究“唐氏綜合癥”等染色體疾病以及研究基因療法的潛力,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature doi: 10.1038/nature12394
Translating dosage compensation to trisomy 21
Jun Jiang, Yuanchun Jing, Gregory J. Cost, Jen-Chieh Chiang, Heather J. Kolpa, Allison M. Cotton, Dawn M. Carone, Benjamin R. Carone, David A. Shivak, Dmitry Y. Guschin, Jocelynn R. Pearl, Edward J. Rebar, Meg Byron, Philip D. Gregory, Carolyn J. Brown, Fyodor D. Urnov, Lisa L. Hall &Jeanne B. Lawrence
Down’s syndrome is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21. We tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST (the X-inactivation gene). Using genome editing with zinc finger nucleases, we inserted a large, inducible XIST transgene into the DYRK1A locus on chromosome 21, in Down’s syndrome pluripotent stem cells. The XIST non-coding RNA coats chromosome 21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a ‘chromosome 21 Barr body’. This provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise. Notably, deficits in proliferation and neural rosette formation are rapidly reversed upon silencing one chromosome 21. Successful trisomy silencing in vitro also surmounts the major first step towards potential development of ‘chromosome therapy’.
