Reprogrammed gene expression in a somatic cell-free extract.
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.
Landsverk
Helga B
HB
Institute of Medical Biochemistry, PO Box 1112 Blindern, University of Oslo, Oslo 0317, Norway.
Håkelien
Anne-Mari
AM
Küntziger
Thomas
T
Robl
James M
JM
Skålhegg
Bjørn S
BS
Collas
Philippe
P
D000107:Acetylation; D000123:Acetyltransferases; D002467:Cell Nucleus / Q000378:metabolism; D002474:Cell-Free System; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D002843:Chromatin; D007376:Interleukin-2; D046911:Macromolecular Substances; D014157:Transcription Factors; D000123:Acetyltransferases