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Transcriptional regulation of lipid biosynthetic genes by FBI‐1 (Pokemon) and SREBP‐1a
Author(s) -
Yoo JungYoon,
Choi WonIl,
Kim YuRi,
Park Hyejin,
Kim YeonSook,
Kim KyungSup,
Hur ManWook
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb9
Subject(s) - sterol regulatory element binding protein , transcription factor , lipogenesis , transcription (linguistics) , activator (genetics) , fatty acid synthase , promoter , gene , microbiology and biotechnology , biology , response element , e box , transcriptional regulation , gene expression , chemistry , biochemistry , linguistics , philosophy
FBI‐1 (also called Pokemon) is a BTB/POZ‐domain proto‐oncogenic transcription factor. Recently, that expression of FBI‐1 was induced in both murine and human preadipocytes differentiation and may play important role in promoting growth arrest and terminal differentiation of preadipocyte. SREBP‐1a is major regulator of adipocyte differentiation and potent transcription activator of the genes related with cholesterol and fatty acid biosynthesis. We investigated whether FBI‐1 affects the transcription controlled by SREBPs. We found that FBI‐1 and SREBP1 interact in vivo and in vitro. Also, the interaction resulted in strong transcription activation of the SREBP responsive 6x SRE‐Luc and fatty acid synthase (FAS) promoter, a key enzyme in lipogenesis in mammals. IP and GST pull‐down experiments with various SREBP1 and FBI‐1 deletion constructs showed that the ZFDBD of FBI‐1 directly interacts with the bHLH domain of SREBP1. Furthermore, we showed that the ZFDBD of FBI‐1 can activate transcription with SREBP‐1a. EMSA and ChIP assays showed that the DNA binding affinity of SREBP‐1 to various SRE and E‐box probes is significantly increased by the presence of ZFDBD of FBI‐1, which may explain increased transcription activation of SREBP target genes by FBI‐1 and SREBP‐1. We propose that FBI‐1 plays an important roles in the transcription activation of lipogenic genes and perhaps also in adipocytes differentiation by increasing DNA binding activity of SREBP‐1.