S-W Qian

Publications (2)8.24 Total impact

• Article: G9a is Transactivated by C/EBPbeta to Facilitate Mitotic Clonal Expansion during 3T3-L1 Preadipocyte Differentiation

  S. F. Li, L. Guo, S. W. Qian, Y. Liu, Y. Y. Zhang, Z. C. Zhang, Y. Zhao, J. Y. Shou, Q. Q. Tang, X. Li
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  ABSTRACT: In 3T3-L1 preadipocyte differentiation, the CCAAT/enhancer-binding protein beta (C/EBPbeta) is an important early transcription factor that activates cell cycle genes during mitotic clonal expansion (MCE), sequentially activating peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer binding protein alpha (C/EBPalpha) during terminal differentiation. Although C/EBPbeta acquires its DNA binding activity via dual phosphorylation at about 12-16h post-induction, the expression of PPARgamma and C/EBPalpha is not induced until 36-72h. The delayed expression of PPARgamma and C/EBPalpha ensures the progression of MCE, but the mechanism responsible for the delay remains elusive. We provide evidence that G9a, a major euchromatic methyltransferase, is transactivated by C/EBPbeta and represses PPARgamma and C/EBPalpha through H3K9 dimethylation of their promoters during MCE. Inhibitor- or siRNA-mediated G9a downregulation modestly enhance PPARgamma and C/EBPalpha expression and adipogenesis in 3T3-L1 preadipocytes. Conversely, forced expression of G9a impairs the accumulation of triglycerides. Thus, this study elucidates an epigenetic mechanism for the delayed expression of PPARgamma and C/EBPalpha.
  Am J Physiol Endocrinol Metab. 01/2013;
• Article: Histone demethylase Kdm4b functions as a co-factor of C/EBPβ to promote mitotic clonal expansion during differentiation of 3T3-L1 preadipocytes.

  L Guo, X Li, J-X Huang, H-Y Huang, Y-Y Zhang, S-W Qian, H Zhu, Y-D Zhang, Y Liu, K-K Wang, Q-Q Tang
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  ABSTRACT: CCAAT/enhancer-binding protein (C/EBP) β is required for both mitotic clonal expansion (MCE) and terminal adipocyte differentiation of 3T3-L1 preadipocytes. Although the role of C/EBPβ in terminal adipocyte differentiation is well defined, its mechanism of action during MCE is not. In this report, histone demethylase Kdm4b, as well as cell cycle genes Cdc45l (cell division cycle 45 homolog), Mcm3 (mini-chromosome maintenance complex component 3), Gins1 (GINS complex subunit 1) and Cdc25c (cell division cycle 25 homolog c), were identified as potential C/EBPβ target genes during MCE by utilizing promoter-wide chromatin immunoprecipitation (ChIP)-on-chip analysis combined with gene expression microarrays. The expression of Kdm4b is induced during MCE and its induction is dependent on C/EBPβ. ChIP, Electrophoretic Mobility Shift Assay (EMSA) and luciferase assay confirmed that the promoter of Kdm4b is bound and activated by C/EBPβ. Knockdown of Kdm4b impaired MCE. Furthermore, Kdm4b interacted with C/EBPβ and was recruited to the promoters of C/EBPβ-regulated cell cycle genes, including Cdc45l, Mcm3, Gins1, and Cdc25c, demethylated H3K9me3 and activated their transcription. These findings suggest a novel feed forward mechanism involving a DNA binding transcription factor (C/EBPβ) and a chromatin regulator (Kdm4b) in the regulation of MCE by controlling cell cycle gene expression.Cell Death and Differentiation advance online publication, 22 June 2012; doi:10.1038/cdd.2012.75.
  Cell death and differentiation 06/2012; · 8.24 Impact Factor