Leukocyte-specific expression of the pp52 (LSP1) promoter is controlled bythe cis-acting pp52 silencer and anti-silencer elements

pp52 (LSP1) is a leukocyte-specific phosphoprotein that binds the cytoskele ton and has been implicated in affecting cytoskeletal remodeling in a varie ty of leukocyte functions, including cell motility and chemotaxis. The expr ession of pp52 is restricted to leukocytes by a 549 bp tissue-specific prom oter. Here, we show that promoter fragments smaller than the 549 bp pp52 pr omoter have activity in fibroblasts where pp52 is not normally expressed. S pecifically, a truncated construct (+1 to -99) functioned as a basal promot er active in leukocytes and fibroblasts. We identified two upstream regions within the 549 bp pp52 promoter responsible for restricting pp52 promoter activity in fibroblasts. These two regions contained a silencer (pp52 NRE) and an anti-silencer (pp52 anti-NRE) with opposing activities controlling p p52 gene expression. The pp52 NRE was active in both leukocytes and fibrobl asts while the pp52 anti-NRE was only active in leukocytes, thereby allowin g pp52 gene transcription in leukocytes but not in fibroblasts. The pp52 NR E was localized to an 89 bp DNA segment between -324 and -235 in the 549 bp pp52 promoter and functioned as an active silencer element in a position a nd orientation independent manner. The pp52 anti-NRE was localized to a 33 bp segment between -383 and -350 of the 549 bp pp52 promoter and acted as a n anti-silencer element against the pp52 NRE, but lacked any intrinsic enha ncing activity on its own. These findings indicate that the tissue specific ity of the pp52 promoter is determined by the pp52 anti-NRE anti-silencer w hich over-rides the general inhibitory activity of the pp52 NRE silencer. ( C) 2001 Elsevier Science B.V. All rights reserved.