Functional analysis of PU.1 domains in monocyte-specific gene regulation.
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.
Nishiyama
Chiharu
C
Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. chinishi@med.juntendo.ac.jp
Nishiyama
Makoto
M
Ito
Tomonobu
T
Masaki
Shigehiro
S
Masuoka
Nobutaka
N
Yamane
Hisakazu
H
Kitamura
Toshio
T
Ogawa
Hideoki
H
Okumura
Ko
K
D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division; D048429:Cell Size; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism*; D009154:Mutation; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1
D015850:Interleukin-6; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1