Molecular and Cellular Biology Graduate Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Nucleic Acids Res. 2011 Jul;39(12):4975-83. doi: 10.1093/nar/gkr079. Epub 2011 Mar 3.
The RNA Pol II transcription complex pauses just downstream of the promoter in a significant fraction of human genes. The local features of genomic structure that contribute to pausing have not been defined. Here, we show that genes that pause are more G-rich within the region flanking the transcription start site (TSS) than RefSeq genes or non-paused genes. We show that enrichment of binding motifs for common transcription factors, such as SP1, may account for G-richness upstream but not downstream of the TSS. We further show that pausing correlates with the presence of a GrIn1 element, an element bearing one or more G4 motifs at the 5'-end of the first intron, on the non-template DNA strand. These results suggest potential roles for dynamic G4 DNA and G4 RNA structures in cis-regulation of pausing, and thus genome-wide regulation of gene expression, in human cells.
RNA 聚合酶 II 转录复合物在人类基因的启动子下游有很大一部分会暂停。但仍未定义导致暂停的基因组结构的局部特征。本文中，作者发现与 RefSeq 基因或非暂停基因相比，在转录起始位点 (TSS) 侧翼的区域中，暂停基因富含 G。作者还发现，常见转录因子（如 SP1）的结合基序的富集可能解释了 TSS 上游而非下游富含 G 的原因。进一步研究发现，暂停与 GrIn1 元件的存在相关，GrIn1 元件在第一个内含子的非模板 DNA 链 5'-端有一个或多个 G4 基序。这些结果表明，动态 G4 DNA 和 G4 RNA 结构可能在人类细胞中转录暂停的顺式调控以及整个基因组范围内的基因表达调控中发挥作用。
