Landsverk Helga B, Håkelien Anne-Mari, Küntziger Thomas, Robl James M, Skålhegg Bjørn S, Collas Philippe
Institute of Medical Biochemistry, PO Box 1112 Blindern, University of Oslo, Oslo 0317, Norway.
EMBO Rep. 2002 Apr;3(4):384-9. doi: 10.1093/embo-reports/kvf064. Epub 2002 Mar 15.
We have developed a somatic cell-free system that remodels chromatin and activates gene expression in heterologous differentiated nuclei. Extracts of stimulated human T cells elicit chromatin binding of transcriptional activators of the interleukin-2 (IL-2) gene, anchoring and activity of a chromatin-remodeling complex and hyperacetylation of the IL-2 promoter in purified exogenous resting T-cell nuclei. The normally repressed IL-2 gene is transcribed in nuclei from quiescent human T cells and from various non-T-cell lines. This demonstrates that somatic cell extracts can be used to reprogram gene expression in differentiated nuclei. In vitro reprogramming may be useful for investigating regulation of gene expression and for producing replacement cells for the treatment of a wide variety of diseases.
我们开发了一种无细胞体细胞系统，该系统可重塑染色质并激活异源分化细胞核中的基因表达。经刺激的人T细胞提取物可引发白细胞介素-2（IL-2）基因转录激活因子与染色质的结合、染色质重塑复合物的锚定和活性，以及纯化的外源性静止T细胞核中IL-2启动子的超乙酰化。正常情况下受到抑制的IL-2基因在静止的人T细胞和各种非T细胞系的细胞核中被转录。这表明体细胞提取物可用于重编程分化细胞核中的基因表达。体外重编程可能有助于研究基因表达的调控，并用于生产替代细胞以治疗多种疾病。
