Manipulating transgenes using a chromosome vector.
Recent technological advances have enabled us to visualize the organization and dynamics of local chromatin structures; however, the comprehensive mechanisms by which chromatin organization modulates gene regulation are poorly understood. We designed a human artificial chromosome vector that allowed manipulation of transgenes using a method for delivering chromatin architectures into different cell lines from human to fish. This methodology enabled analysis of de novo construction, epigenetic maintenance and changes in the chromatin architecture of specific genes. Expressive and repressive architectures of human STAT3 were established from naked DNA in mouse embryonic stem cells and CHO cells, respectively. Delivery of STAT3 within repressive architecture to embryonic stem cells resulted in STAT3 activation, accompanied by changes in DNA methylation. This technology for manipulating a single gene with a specific chromatin architecture could be utilized in applied biology, including stem cell science and regeneration medicine.
Ikeno
Masashi
M
School of Medicine, Keio University, Shinanomachi, Shinjuku-ku, Tokyo, Japan. mikeno@fujita-hu.ac.jp
Suzuki
Nobutaka
N
Hasegawa
Yoshinori
Y
Okazaki
Tsuneko
T
D000818:Animals; D016466:CHO Cells; D002843:Chromatin / Q000737:chemistry; D022222:Chromosomes, Artificial, Human / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D051381:Rats; D050796:STAT3 Transcription Factor / Q000235:genetics; D019076:Transgenes
D002843:Chromatin; D050796:STAT3 Transcription Factor