Studies On The Molecular Mechanism Of Nuclear Actin In Regulating The Function Of SATB1

Gene expression can be regulated at three levels, including DNA sequence, chromatin and nuclear level. Regulation at the sequence level is studied mostly., and the basic question is whether single gene or cluster genes are regulated. Regulation at the chromatin level reflects chromatin's different functional stations .The regulation at DNA sequence level and chromatin level take place in the nucleus and they are influenced by the structure of the nucleus. Some researches have shown that SATB1 is an important genome organizer.Specific AT-rich binding protein1( SATB1) is a T-cell-specific transcription factor and expressed mostly in thymocytes. It was shown to regulate gene expression by selectively tethering BURs to the nuclear matrix. Previous studies have demonstrated that SATB1 can bind to the IL-2 gene promoter and inhibit IL-2 gene expression. Other studies showed that SATB's function of inhibiting gene expression was based on its binding to the nuclear matrix. However, whether the binding is direct or not is still not clear.Actin is a highly conserved protein, and it exists in mostly all eukaryotic cells. At the beginning, people just found actin in the cytoplasm, and function in cell movement, cell struction maintence, cell division and so on. Recently, Actin is also found in the nucleus and founctions in many nuclear processes, such as DNA replication, DNA transcription, and DNA repair and RNA transportation. A great many of studies have shown that Actin may be a component of the nuclear matrix. Whether Actin in the nuclear matrix could influence SATB1 targeted to the nuclear matrix.We used LatB to treatment Jurkat cells,then did cell fractionation, and found that SATB1 in the nuclear matrix is reduced after inhibition of actin polymerization . And this reflected that Actin could influence distribution of SATB1 in the nuclear matrix. Furtherly , we identified F-actin, not G-actin, as a candidate for interacting with SATB1 through GST pull-down in vitro and immunoprecipitation in vivo. Such interaction mediates SATB1 binding to the nuclear matrix. Preventing Actin's polymerization can relieve IL-2 gene transcription repression mediated by SATB1. These data suggest that Actin polymerization can influence SATB1 targeted to the nuclear matrix and thus influence gene regulation.