Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription.

Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription.
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DOI:
10.1038/nsmb.3424
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发表时间:
2017-07
影响因子:
16.8
通讯作者:
Ruthenburg AJ
Ruthenburg AJ
中科院分区:
生物学1区
文献类型:
--
作者:
Werner MS;Sullivan MA;Shah RN;Nadadur RD;Grzybowski AT;Galat V;Moskowitz IP;Ruthenburg AJ

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我们最近描述了一类新的长非编码RNA,其定义为特别紧密的染色质缔合,其存在与HEK293细胞中附近基因的表达密切相关。在这里,我们严格审查这类染色质富集RNA(cheRNA)的一般性和顺式增强子机制。CheRNA在很大程度上是细胞类型特异性的,并且仍然是用于预测所检查的所有细胞类型中的顺式基因转录的最有效的染色质签名。三种cheRNA的靶向缺失降低了它们邻居的基因表达,表明潜在的共激活子功能。一个cheRNA远端靶基因对的单分子FISH表明空间重叠与染色体成环中的作用一致。在另一个实例中,cheRNA HIDALGO通过促进与下游增强子的接触在红细胞分化期间刺激胎儿血红蛋白HBG1基因。我们的研究结果表明,许多cheRNA激活近端,谱系特异性基因转录。
We recently described a new class of long noncoding RNA defined by especially tight chromatin association, whose presence is strongly correlated with expression of nearby genes in HEK293 cells. Here we critically examine the generality and cis-enhancer mechanism of this class of chromatin enriched RNA (cheRNA). CheRNA are largely cell-type specific, and remain the most effective chromatin signature for predicting cis-gene transcription in all cell types examined. Targeted depletion of three cheRNAs decreases gene expression of their neighbors, indicating potential co-activator function. Single-molecule FISH of one cheRNA-distal target gene pair suggests spatial overlap consistent with a role in chromosome looping. In another example, the cheRNA HIDALGO stimulates the fetal hemoglobin HBG1 gene during erythroid differentiation by promoting contacts to a downstream enhancer. Our results suggest that many cheRNAs activate proximal, lineage-specific gene transcription.
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