Suppressive effects of transcription factor GATA-1 on cell type-specific gene expression in dendritic cells.
To evaluate the effects of the transcription factor GATA-1 on determining cell fate between dendritic cell (DC) and mast cell (MC) lineages, GATA-1 was exogenously expressed in bone marrow-derived (BM) DCs. Exogenous expression of GATA-1 by a retrovirus in BMDCs inhibited expression of CD11c, CD80, CD86, and major histocompatibility complex class II with suppression of antigen-presenting ability and morphological changes toward granulocyte-like cells. Transcription of MC proteases and c-kit was markedly upregulated by GATA-1. Expression of IRF-4 and -8 was markedly suppressed, whereas PU.1 mRNA level was not affected by GATA-1. Chromatin immunoprecipitation assay showed that recruitment of PU.1 on the IRF-8 promoter was reduced in GATA-1-expressing DCs. These results indicate that GATA-1 suppresses PU.1 function but not PU.1 transcription. Thus, GATA-1 appears to determine cell fate by regulating several cell-specific transcription factors.
Shimokawa
Naomi
N
Atopy (Allergy) Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Nishiyama
Chiharu
C
Nakano
Nobuhiro
N
Maeda
Keiko
K
Suzuki
Ryuyo
R
Hara
Mutsuko
M
Fukai
Tatsuo
T
Tokura
Tomoko
T
Miyajima
Hiroaki
H
Nakao
Atsuhito
A
Ogawa
Hideoki
H
Okumura
Ko
K
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099185:Interferon Regulatory Factor-8
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D050982:GATA1 Transcription Factor; D050835:Interferon Regulatory Factors; D012333:RNA, Messenger; D000099185:Interferon Regulatory Factor-8; C494689:Gata1 protein, mouse
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