Functional analysis of PU.1 domains in monocyte-specific gene regulation

Open Access
Publisher Website
Google Scholar
Abstract
The Ets family transcription factor PU.1 is required for the development of various lymphoid and myeloid cell lineages, and regulates the expression of several genes in a cell type‐specific manner. Recently we found that overproduction of PU.1 in mouse bone marrow‐derived mast cell progenitors induced the expression of monocyte‐specific genes. This prompted us to analyze the functions of each domain of PU.1 in monocyte‐specific gene expression, using transfection of mast cell progenitors with a series of retrovirus vectors for overexpression of various truncation mutants. Both the acidic region and the Ets domain of PU.1 were required for expression of monocyte‐specific genes, and for enhanced interleukin‐6 production in response to lipopolysaccharide. The Gln‐rich region was suggested to be involved in expression of both MHC class II and F4/80. On the other hand, when PU.1 protein lacking the PEST domain was produced in the progenitor cells, expression of monocyte‐specific genes was substantially enhanced, suggesting that the PEST domain plays a negative role in monocyte‐specific gene expression.