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Transcriptional Activation of Lipogenic Genes by Insulin/Feeding
Author(s) -
Sul Hei Sook
Publication year - 2019
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.2019.33.1_supplement.346.3
Subject(s) - lipogenesis , chromatin , chromatin remodeling , demethylase , histone , transcriptional regulation , fatty acid synthase , transcription factor , biology , chemistry , biochemistry , microbiology and biotechnology , gene
Insulin treatment or feeding a high carbohydrate diet causes a marked increase in fatty acid and fat synthesis and enzymes involved in lipogenesis are coordinately induced. We are studying transcriptional activation of lipogenic genes, employing fatty acid synthase (FAS) as a model system. We defined insulin response element at ‐65 E‐box and USF binding at this site for transcriptional activation by insulin. USF and SREBP‐1c, by binding at adjacent sites, directly interact and function together. We identified various other components of the USF complex and their posttranslational modifications by feeding/insulin treatment. USF‐1 recruits and is phosphorylated by DNA‐PK allowing recruitment and acetylation by P/CAF, resulting in the FAS promoter activation, whereas, in fasting, USF‐1 is deacetylated by HDAC9. USF also recruits Brg1/Brm‐associated factor (BAF) 60c that functions as a specific chromatin‐remodeling component for lipogenic gene transcription. In response to insulin, BAF60c is phosphorylated at S247 by atypical PKCζ/λ, which causes translocation of BAF60c to the nucleus, allowing a direct interaction with USF‐1. Thus, BAF60c is recruited to form the lipoBAF complex to remodel chromatin structure. Recently, we also found that by direct interaction USF‐1 recruits specific histone demethylase for histone modification and transcriptional activation of various lipogenic genes. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .