Department of Genetics, The Anlyan Center, Yale University School of Medicine, New Haven, CT, USA.
EMBO J. 2010 Oct 6;29(19):3260-71. doi: 10.1038/emboj.2010.204. Epub 2010 Aug 31.
DNA replication, repair, transcription and chromatin structure are intricately associated nuclear processes, but the molecular links between these events are often obscure. In this study, we have surveyed the protein complexes that bind at β-globin locus control region, and purified and characterized the function of one such multiprotein complex from human erythroleukemic K562 cells. We further validated the existence of this complex in human CD34+ cell-derived normal erythroid cells. This complex contains ILF2/ILF3 transcription factors, p300 acetyltransferase and proteins associated with DNA replication, transcription and repair. RNAi knockdown of ILF2, a DNA-binding component of this complex, abrogates the recruitment of the complex to its cognate DNA sequence and inhibits transcription, histone acetylation and usage of the origin of DNA replication at the β-globin locus. These results imply a direct link between mammalian DNA replication, transcription and histone acetylation mediated by a single multiprotein complex.
DNA 复制、修复、转录和染色质结构是与核过程密切相关的，但这些事件之间的分子联系往往不清楚。在这项研究中，我们调查了与β-珠蛋白基因调控区结合的蛋白质复合物，并从人红白血病 K562 细胞中纯化和鉴定了其中一种多蛋白复合物的功能。我们进一步验证了该复合物在人 CD34+细胞来源的正常红细胞中的存在。该复合物包含 ILF2/ILF3 转录因子、p300 乙酰转移酶以及与 DNA 复制、转录和修复相关的蛋白质。该复合物的 DNA 结合成分 ILF2 的 RNAi 敲低会破坏该复合物与自身同源 DNA 序列的募集，并抑制转录、组蛋白乙酰化以及在β-珠蛋白基因座处的 DNA 复制起点的使用。这些结果表明，哺乳动物的 DNA 复制、转录和组蛋白乙酰化之间存在直接联系，由单个多蛋白复合物介导。
