Temporal profiles of appearance of DNase I hypersensitive sites associated with the ovine b-lactoglobulin gene differ in sheep and transgenic mice

Abstract

The ovine milk protein β-lactoglobulin is expressed in a distinct temporal pattern during lactogenesis. This expression pattern is reflected in the temporal profile of appearance of DNase I hypersensitive sites (HS) associated with the β-lactoglobulin gene in the mammary gland. Specifically, HSIV and HSV are present prior to the first major increase in expression, which occurs at mid-pregnancy, while HSI displays the converse profile, being detected after mid-pregnancy and during lactation. The extent of DNase I digestion at HSIII, encompassing the promoter region, reflects the level of β-lactoglobulin expression. In transgenic mouse mammary chromatin, β-lactoglobulin transgenes display the same set of DNase I hypersensitive sites as in sheep mammary chromatin. The temporal profile, however, differs from that seen in sheep: notably, HSIV and HSV are detected during lactation. The fact that β-lactoglobulin transgenes lacking HSIV and HSV are expressed but display a reduced transcription rate per integrated copy is compatible with a functional role for these regions. This suggests that HSIV and HSV may increase the likelihood of high-level transgene expression.