The First Exon of the Rat Aldolase C Gene Is Essential for Restoring the Chromatin Structure in Transgenic Mice

Arai, Yuji; Sugama, Takako; Hashido, Kazuo; Ohishi, Sachiko; Mukai, Tsunehiro
January 1997
Journal of Biochemistry;1997, Vol. 122 Issue 5, p927
Academic Journal
A 13-kb fragment of the rat aldolase C gene contains sufficient information for gene expression. Transgenic mice carrying the 13-kb fragment showed restoration of chromatin structure and tissue-specific, copy number-dependent expression. To localize the regulatory elements responsible for restoring chromatin structure, several mutated constructs were used to produce transgenic mice. Three activities were examined: recreation of DNase hypersensitive sites, restoration of methylation status, and copy number-dependent expression. Deletions of the 3′-flanking region did not affect those activities. Deletion of seven introns affected the mRNA levels but not the restoration of the chromatin structure. The insertion of the LacZ gene into the first exon of the transgene interfered with both the restoration of the chromatin structure and the copy number-dependent expression in transgenic mice. DNase I footprinting assays revealed that brain-specific factors bind to the sequence disrupted by the LacZ insertion. These results suggest that the sequence in the first exon is essential for restoring the chromatin structure of the rat aldolase C gene.


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