From the Division of Metabolic Diseases, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
J Biol Chem. 2010 Sep 24;285(39):29729-37. doi: 10.1074/jbc.M110.153858. Epub 2010 Jul 9.
The multiprotein Mediator complex is an important regulator of RNA polymerase II-dependent genes in eukaryotic cells. In contrast to the situation in many other eukaryotes, the conserved Med15 protein is not a stable component of Mediator isolated from fission yeast. We here demonstrate that Med15 exists in a protein complex together with Hrp1, a CHD1 ATP-dependent chromatin-remodeling protein. The Med15-Hrp1 subcomplex is not a component of the core Mediator complex but can interact with the L-Mediator conformation. Deletion of med15(+) and hrp1(+) causes very similar effects on global steady-state levels of mRNA, and genome-wide analyses demonstrate that Med15 associates with a distinct subset of Hrp1-bound gene promoters. Our findings therefore indicate that Mediator may directly influence histone density at regulated promoters.
多蛋白 Mediator 复合物是真核细胞中 RNA 聚合酶 II 依赖性基因的重要调节剂。与许多其他真核生物的情况不同,保守的 Med15 蛋白不是裂殖酵母中分离出的 Mediator 的稳定成分。我们在这里证明 Med15 与 CHD1 ATP 依赖性染色质重塑蛋白 Hrp1 一起存在于蛋白质复合物中。Med15-Hrp1 亚复合物不是核心 Mediator 复合物的组成部分,但可以与 L-Mediator 构象相互作用。med15(+)和 hrp1(+)的缺失对 mRNA 的全局稳态水平有非常相似的影响,全基因组分析表明 Med15 与一组不同的 Hrp1 结合基因启动子相关联。因此,我们的研究结果表明 Mediator 可能直接影响调节启动子处的组蛋白密度。