SEVERE POSITION EFFECTS IMPOSED ON A 1 KB MOUSE WHEY ACIDIC PROTEIN GENE PROMOTER ARE OVERCOME BY HETEROLOGOUS MATRIX ATTACHMENT REGIONS

Matrix attachment regions (MARs) have been shown to participate in the insulation of transcription elements from surrounding chromatin in ti ssue culture cells and transgenic mice. A whey acidic protein (WAP) tr ansgene containing 1 kb promoter sequence was active in mammary tissue from 1 out of 17 lines of mice, demonstrating that the transcription elements were highly susceptible to position effects. To test whether MARs could insulate this WAP gene promoter and thereby restore transcr iption, we ligated MARs from the chicken lysozyme gene to the WAP tran sgene. Seven of the nine lines generated exhibited WAP transgene activ ity, expression was confined to mammary tissue, and correct regulation was observed in three of the four lines analyzed. This study provides strong additional evidence that the MAR fragments from the chicken ly sozyme gene have the capacity to insulate transgenes from severe posit ion effects. (C) 1996 Wiley-Liss, Inc.