[PDF][PDF] Histone methylation regulator PTIP is required for PPARγ and C/EBPα expression and adipogenesis

YW Cho, SH Hong, Q Jin, L Wang, JE Lee, O Gavrilova… - Cell metabolism, 2009 - cell.com
YW Cho, SH Hong, Q Jin, L Wang, JE Lee, O Gavrilova, K Ge
Cell metabolism, 2009cell.com
Summary PPARγ and C/EBPα cooperate to control preadipocyte differentiation
(adipogenesis). However, the factors that regulate PPARγ and C/EBPα expression during
adipogenesis remain largely unclear. Here, we show PTIP, a protein that associates with
histone H3K4 methyltransferases, regulates PPARγ and C/EBPα expression in mouse
embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs
leads to marked decreases of PPARγ expression and PPARγ-stimulated C/EBPα …
Summary
PPARγ and C/EBPα cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARγ and C/EBPα expression during adipogenesis remain largely unclear. Here, we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARγ and C/EBPα expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARγ expression and PPARγ-stimulated C/EBPα expression. Further, PTIP is essential for induction of PPARγ and C/EBPα expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARγ and C/EBPα promoters. Accordingly, PTIP−/− MEFs and preadipocytes all show striking defects in adipogenesis. Rescue of the adipogenesis defect in PTIP−/− MEFs requires coexpression of PPARγ and C/EBPα. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight. Thus, by regulating PPARγ and C/EBPα expression, PTIP plays a critical role in adipogenesis.
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