Shur Irena, Solomon Ronit, Benayahu Dafna
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Israel.
Stem Cells. 2006 May;24(5):1288-93. doi: 10.1634/stemcells.2005-0300.
The newly identified protein chromatin-related mesenchymal modulator (CReMM) is expressed by marrow stromal progenitors in vivo and ex vivo. CReMM belongs to a recently identified subgroup of chromodomain helicase-DNA-binding proteins composed of multiple domains including chromodomains, SNF2/ATPase, helicase-C domain, SANT, and A/T-hook-DNA binding domain. Chromatin immunoprecipitation assay was applied to follow the dynamics of CReMM binding to A/T-rich regions on promoters of genes that play a role in osteoblast maturation. CReMM interaction with BMP4 and biglycan promoters in the marrow stromal cells was challenged with transforming growth factor-beta. Treatment with 17beta-estradiol enhanced the binding to estrogen receptor and abolished binding to the prolactin receptor promoters; CReMM interaction with osteocalcin promoter was identified constantly. CReMM binding to the analyzed endogenous promoters suggests its direct role in the transcriptional program activated during osteogenic cell differentiation, which may be a useful tool for following the molecular mechanism of the "stemness" of mesenchymal cells.
新鉴定出的蛋白质染色质相关间充质调节剂（CReMM）在体内和体外均由骨髓基质祖细胞表达。CReMM属于最近鉴定出的一组包含多个结构域的染色质结构域解旋酶-DNA结合蛋白亚组，这些结构域包括染色质结构域、SNF2/ATP酶、解旋酶-C结构域、SANT和A/T-钩-DNA结合结构域。应用染色质免疫沉淀试验来追踪CReMM与在成骨细胞成熟中起作用的基因启动子上富含A/T区域的结合动态。用转化生长因子-β对骨髓基质细胞中CReMM与骨形态发生蛋白4（BMP4）和双糖链蛋白聚糖启动子间的相互作用进行了验证。用17β-雌二醇处理增强了与雌激素受体的结合，并消除了与催乳素受体启动子的结合；持续鉴定出CReMM与骨钙素启动子的相互作用。CReMM与所分析的内源性启动子的结合表明其在成骨细胞分化过程中激活的转录程序中起直接作用，这可能是追踪间充质细胞“干性”分子机制的有用工具。
