First Author | Zhang YY | Year | 2011 |
Journal | Mol Biol Cell | Volume | 22 |
Issue | 13 | Pages | 2165-74 |
PubMed ID | 21562223 | Mgi Jnum | J:183072 |
Mgi Id | MGI:5317409 | Doi | 10.1091/mbc.E10-11-0912 |
Citation | Zhang YY, et al. (2011) Transcriptional activation of histone H4 by C/EBPbeta during the mitotic clonal expansion of 3T3-L1 adipocyte differentiation. Mol Biol Cell 22(13):2165-74 |
abstractText | CCAAT enhancer binding protein beta (C/EBPbeta) is required for both mitotic clonal expansion (MCE) and terminal differentiation during the 3T3-L1 adipocyte differentiation program. Whereas the mechanism of C/EBPbeta during terminal differentiation is well understood, the mechanism of C/EBPbeta in MCE is not. We provide evidence that histone H4, the most conserved cell cycle-related histone, the change of which is strictly correlated with DNA content change during the cell cycle, is transcriptionally activated by C/EBPbeta during MCE. Expression of histone H4 is increased at 16 h after induction when 3T3-L1 preadipocytes synchronously reenter S phase, which is correlated with the sequential phosphorylation and activation of C/EBPbeta, and expression was partially suppressed when A-C/EBP (dominant negative for C/EBP protein) was overexpressed. One C/EBP-binding site was identified in one of the histone H4 gene promoters (hist4h4), confirmed by both electrophoretic mobility shift assay and chromatin immunoprecipitation assay. C/EBP-binding sites were also found in 9 of 11 other histone H4 promoters, which can also be transactivated by C/EBPbeta. Knockdown of C/EBPbeta by stealth small interfering RNA partially decreased H4 gene expression and arrested cells in G1 phase as indicated by bromodeoxyuridine incorporation and fluorescence-activated cell sorting analysis of DNA content. This study provides new insights into why C/EBPbeta is required for MCE during 3T3-L1 adipocyte differentiation and why C/EBPbeta plays important roles in the proliferation of other cell types. |