Howard Hughes Medical Institute, Boston, MA 02115, USA.
Cell. 2010 Jul 9;142(1):133-43. doi: 10.1016/j.cell.2010.05.028.
Recent genome-wide studies have demonstrated that pausing of RNA polymerase II (Pol II) occurred on many vertebrate genes. By genetic studies in the zebrafish tif1gamma mutant moonshine we found that loss of function of Pol II-associated factors PAF or DSIF rescued erythroid gene transcription in tif1gamma-deficient animals. Biochemical analysis established physical interactions among TIF1gamma, the blood-specific SCL transcription complex, and the positive elongation factors p-TEFb and FACT. Chromatin immunoprecipitation assays in human CD34(+) cells supported a TIF1gamma-dependent recruitment of positive elongation factors to erythroid genes to promote transcription elongation by counteracting Pol II pausing. Our study establishes a mechanism for regulating tissue cell fate and differentiation through transcription elongation.
最近的全基因组研究表明,RNA 聚合酶 II(Pol II)在许多脊椎动物基因上发生暂停。通过在斑马鱼 tif1gamma 突变体 moonshine 中的遗传研究,我们发现 Pol II 相关因子 PAF 或 DSIF 的功能丧失可挽救 tif1gamma 缺陷动物中红细胞基因的转录。生化分析确立了 TIF1gamma、血液特异性 SCL 转录复合物以及正延伸因子 p-TEFb 和 FACT 之间的物理相互作用。在人 CD34(+)细胞中的染色质免疫沉淀分析支持 TIF1gamma 依赖性募集正延伸因子到红细胞基因,以通过抵消 Pol II 暂停来促进转录延伸。我们的研究建立了一种通过转录延伸调节组织细胞命运和分化的机制。