Association of the Long Non-coding RNA Steroid Receptor RNA Activator (SRA) with TrxG and PRC2 Complexes.
Association of the Long Non-coding RNA Steroid Receptor RNA Activator (SRA) with TrxG and PRC2 Complexes.
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DOI：
10.1371/journal.pgen.1005615
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发表时间：
2015-10
期刊：
影响因子：
4.5
通讯作者：
Felsenfeld G
中科院分区：
文献类型：
--
作者：
Wongtrakoongate P;Riddick G;Fucharoen S;Felsenfeld G
Long non-coding RNAs (lncRNAs) have been recognized as key players in transcriptional regulation. We show that the lncRNA steroid receptor RNA activator (SRA) participates in regulation through complex formation with trithorax group (TrxG) and polycomb repressive complex 2 (PRC2) complexes. Binding of the SRA-associated RNA helicase p68 preferentially stabilizes complex formation between SRA and a TrxG complex but not PRC2. In human pluripotent stem cells NTERA2, SRA binding sites that are also occupied by p68 are significantly enriched for H3K4 trimethylation. Consistent with its ability to interact with TrxG and PRC2 complexes, some SRA binding sites in human pluripotent stem cells overlap with bivalent domains. CTCF sites associated with SRA appear also to be enriched for bivalent modifications. We identify NANOG as a transcription factor directly interacting with SRA and co-localizing with it genome-wide in NTERA2. Further, we show that SRA is important for maintaining the stem cell state and for reprogramming of human fibroblasts to achieve the pluripotent state. Our results suggest a mechanism whereby the lncRNA SRA interacts with either TrxG or PRC2. These complexes may then be recruited by various DNA binding factors to deliver either activating or silencing signals, or both, to establish bivalent domains. Long non-coding RNAs (lncRNAs) can play an important role in regulation of gene expression. In a number of cases, individual lncRNAs have been shown to interact with either the trithorax group (TrxG) or polycomb repressive complex 2 (PRC2) protein complexes, which deliver histone modifications associated respectively with transcriptionally active or inactive chromatin. Here we show that the lncRNA, SRA, unusually forms complexes with both TrxG and PRC2 complexes. Consistent with this property, some SRA binding sites in human pluripotent stem cells overlap with bivalent domains, which carry both kinds of histone modifications. We find that SRA complexed with the helicase protein, p68, shows enhanced binding of TrxG complex, but not of PRC2. This is reflected in genome wide enriched ‘activating’ histone modifications at SRA sites also occupied by p68. We show that in human pluripotent stem cells SRA also interacts with NANOG, a principal determinant of pluripotency, and is important for maintenance of the pluripotent state. SRA may be involved in the delivery of histone modifications associated with either activation or silencing of gene expression, and in some cases could deliver both.
