Werner Michael S, Sullivan Matthew A, Shah Rohan N, Nadadur Rangarajan D, Grzybowski Adrian T, Galat Vasiliy, Moskowitz Ivan P, Ruthenburg Alexander J
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois, USA.
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.
Nat Struct Mol Biol. 2017 Jul;24(7):596-603. doi: 10.1038/nsmb.3424. Epub 2017 Jun 19.
We recently described a new class of long noncoding RNAs (lncRNAs) that are distinguished by especially tight chromatin association and whose presence is strongly correlated to expression of nearby genes. Here, we examine the cis-enhancer mechanism of this class of chromatin-enriched RNA (cheRNA) across multiple human cell lines. cheRNAs are largely cell type specific and provide the most reliable chromatin signature to predict cis-gene transcription in every human cell type examined. Targeted depletion of three cheRNAs decreases expression of their neighboring genes, indicating potential co-activator function, and single-molecule fluorescence in situ hybridization (smFISH) of one cheRNA-distal target gene pair suggests a spatial overlap consistent with a role in chromosome looping. Additionally, the cheRNA HIDALGO stimulates the fetal hemoglobin subunit gamma 1 (HBG1) gene during erythroid differentiation by promoting contacts to a downstream enhancer. Our results suggest that multiple cheRNAs activate proximal lineage-specific gene transcription.
我们最近描述了一类新的长链非编码RNA（lncRNA），其特点是与染色质的结合特别紧密，并且它们的存在与附近基因的表达密切相关。在此，我们在多种人类细胞系中研究了这类染色质富集RNA（cheRNA）的顺式增强子机制。cheRNA在很大程度上具有细胞类型特异性，并且为预测所检测的每种人类细胞类型中的顺式基因转录提供了最可靠的染色质特征。靶向敲除三种cheRNA会降低其邻近基因的表达，表明其具有潜在的共激活功能，并且对一对cheRNA-远端靶基因进行的单分子荧光原位杂交（smFISH）显示出空间重叠，这与在染色体环化中的作用一致。此外，cheRNA HIDALGO在红细胞分化过程中通过促进与下游增强子的接触来刺激胎儿血红蛋白亚基γ1（HBG1）基因。我们的结果表明，多种cheRNA可激活近端谱系特异性基因转录。
