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Association of the Long Non-coding RNA Steroid Receptor RNA Activator (SRA) with TrxG and PRC2 Complexes


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.


Vyšlo v časopise: Association of the Long Non-coding RNA Steroid Receptor RNA Activator (SRA) with TrxG and PRC2 Complexes. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005615
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005615

Souhrn

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.


Zdroje

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