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Publication : A DNA insulator prevents repression of a targeted X-linked transgene but not its random or imprinted X inactivation.

First Author  Ciavatta D Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  26 Pages  9958-63
PubMed ID  16777957 Mgi Jnum  J:111065
Mgi Id  MGI:3652686 Doi  10.1073/pnas.0603754103
Citation  Ciavatta D, et al. (2006) A DNA insulator prevents repression of a targeted X-linked transgene but not its random or imprinted X inactivation. Proc Natl Acad Sci U S A 103(26):9958-63
abstractText  Some genes on the inactive X chromosome escape silencing. One possible escape mechanism is that heterochromatization during X inactivation can be blocked by boundary elements. DNA insulators are candidates for blocking because they shield genes from influences of their chromosomal environment. To test whether DNA insulators can act as boundaries on the X chromosome, we inserted into the mouse X-linked Hprt locus a GFP transgene flanked with zero, one, or two copies of a prototypic vertebrate insulator from the chicken beta-globin locus, chicken hypersensitive site 4, which contains CCCTC binding factor binding sites. On the active X chromosome the insulators blocked repression of the transgene, which commences during early development and persists in adults, in a copy number-dependent manner. CpG methylation of the transgene correlated inversely with expression, but the insulators on the active X chromosome were not methylated. On the inactive X chromosome, insulators did not block random or imprinted X inactivation of the transgene, and both the insulator and transgene were almost completely methylated. Thus, the chicken hypersensitive site 4 DNA insulator is sufficient to protect an X-linked gene from repression during development but not from X inactivation.
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