Pii: S0378-1119(01)00430-9

pp52 (LSP1) is a leukocyte-speci®c phosphoprotein that binds the cytoskeleton and has been implicated in affecting cytoskeletal remodeling in a variety of leukocyte functions, including cell motility and chemotaxis. The expression of pp52 is restricted to leukocytes by a 549 bp tissue-speci®c promoter. Here, we show that promoter fragments smaller than the 549 bp pp52 promoter have activity in ®broblasts where pp52 is not normally expressed. Speci®cally, a truncated construct (11 to 299) functioned as a basal promoter active in leukocytes and ®broblasts. We identi®ed two upstream regions within the 549 bp pp52 promoter responsible for restricting pp52 promoter activity in ®broblasts. These two regions contained a silencer (pp52 NRE) and an anti-silencer (pp52 anti-NRE) with opposing activities controlling pp52 gene expression. The pp52 NRE was active in both leukocytes and ®broblasts while the pp52 anti-NRE was only active in leukocytes, thereby allowing pp52 gene transcription in leukocytes but not in ®broblasts. The pp52 NRE was localized to an 89 bp DNA segment between 2324 and 2235 in the 549 bp pp52 promoter and functioned as an active silencer element in a position and orientation independent manner. The pp52 anti-NRE was localized to a 33 bp segment between 2383 and 2350 of the 549 bp pp52 promoter and acted as an anti-silencer element against the pp52 NRE, but lacked any intrinsic enhancing activity on its own. These ®ndings indicate that the tissue speci®city of the pp52 promoter is determined by the pp52 anti-NRE anti-silencer which over-rides the general inhibitory activity of the pp52 NRE silencer. q 2001 Elsevier Science B.V. All rights reserved.