Belotserkovskaya Rimma, Oh Sangtaek, Bondarenko Vladimir A, Orphanides George, Studitsky Vasily M, Reinberg Danny
Howard Hughes Medical Institute, Department of Biochemistry, Division of Nucleic Acids Enzymology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Science. 2003 Aug 22;301(5636):1090-3. doi: 10.1126/science.1085703.
The FACT (facilitates chromatin transcription) complex is required for transcript elongation through nucleosomes by RNA polymerase II (Pol II) in vitro. Here, we show that FACT facilitates Pol II-driven transcription by destabilizing nucleosomal structure so that one histone H2A-H2B dimer is removed during enzyme passage. We also demonstrate that FACT possesses intrinsic histone chaperone activity and can deposit core histones onto DNA. Importantly, FACT activity requires both of its constituent subunits and is dependent on the highly acidic C terminus of its larger subunit, Spt16. These findings define the mechanism by which Pol II can transcribe through chromatin without disrupting its epigenetic status.
FACT(促进染色质转录)复合物是体外RNA聚合酶II(Pol II)通过核小体进行转录延伸所必需的。在此,我们表明FACT通过破坏核小体结构促进Pol II驱动的转录,使得在酶通过期间一个组蛋白H2A-H2B二聚体被移除。我们还证明FACT具有内在的组蛋白伴侣活性,并且能够将核心组蛋白沉积到DNA上。重要的是,FACT活性需要其两个组成亚基,并且依赖于其较大亚基Spt16的高度酸性C末端。这些发现定义了Pol II能够转录通过染色质而不破坏其表观遗传状态的机制。