<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Long non-coding RNA KHPS1 drives a regulatory cascade which activates expression of the protooncogene SPHK1"^^ . "Numerous long noncoding RNAs (lncRNAs) have been discovered, however only a small\r\nnumber of lncRNAs have been explored with respect to their function and little is known how\r\nthey operate at chromatin. In this study, the function of an E2F1-regulated lncRNA, termed\r\nKHPS1, has been investigated. KHPS1 is transcribed in antisense orientation from the SPHK1\r\n(Sphingosine kinase 1) promoter which in sense orientation directs transcription of SPHK1\r\nmRNA. The results demonstrate that KHPS1 activates SPHK1 transcription by recruiting\r\nhistone acetyltransferase p300 and the transcription factor E2F1 to the SPHK1 enhancer.\r\nBinding of p300 and E2F1 is required for transcription of an enhancer-derived RNA, eRNASphk1.\r\nTranscription of eRNA-Sphk1 evicts CTCF, a factor that insulates the SPHK1 enhancer\r\nfrom the SPHK1 promoter and facilitates SPHK1 expression.\r\nImportantly, the direct association of KHPS1 with a homopurine stretch upstream at the SPHK1\r\nenhancer is essential for SPHK1 expression. Binding of KHPS1 to the SPHK1 enhancer is\r\nmediated via Hoogsteen base pairing, forming RNA-DNA-DNA triplex structure. Tethering\r\nKHPS1 and associated p300 and E2F1 to the SPHK1 enhancer is a prerequisite for activation\r\nof eRNA-Sphk1 transcription and expression of SPHK1. The functional relevance of triplex\r\nformation was further studied using reporter plasmids which mimic KHPS1-dependent\r\ntranscription activation of SPHK1. Deletion or mutation of the triplex forming region (TFR)\r\nattenuated recruitment of p300 and E2F1 and compromised transcription of eRNA-Sphk1.\r\nReplacement of the TFR by foreign triplex-forming motifs from lncRNAs MEG3 or Fendrr\r\nfunctionally replaced the TFR of SPHK1, i.e. activated eRNA-Sphk1 transcription. Ectopic\r\nKHPS1 with the TFR of MEG3 targeted E2F1 and p300 to the MEG3 target gene TGFBR1,\r\nunderscoring the functional relevance of triplex-forming sequences. Genomic deletion of the\r\nTFR or intervention of KHPS1 binding to DNA by ectopic TFR-containing RNA decreased\r\nSPHK1 expression and impaired cell viability. Collectively, the results unravel a triplexdependent\r\nregulatory feed-forward mechanism, involving lncRNA-mediated activation of\r\neRNA which enhances expression of its target gene. The results underscore the pivotal role of\r\ntriplex formation in transcription control, supporting a model whereby lncRNAs tethered to\r\nspecific loci serve as sequence-specific molecular anchors."^^ . "2019" . . . . . . . "Alena"^^ . "Blank-Giwojna"^^ . "Alena Blank-Giwojna"^^ . . . . . . "Long non-coding RNA KHPS1 drives a regulatory cascade which activates expression of the protooncogene SPHK1 (PDF)"^^ . . . "Blank-Giwojna_PhD thesis.pdf"^^ . . . "Long non-coding RNA KHPS1 drives a regulatory cascade which activates expression of the protooncogene SPHK1 (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Long non-coding RNA KHPS1 drives a regulatory cascade which activates expression of the protooncogene SPHK1 (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Long non-coding RNA KHPS1 drives a regulatory cascade which activates expression of the protooncogene SPHK1 (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Long non-coding RNA KHPS1 drives a regulatory cascade which activates expression of the protooncogene SPHK1 (Other)"^^ . . . . . . "small.jpg"^^ . . . "Long non-coding RNA KHPS1 drives a regulatory cascade which activates expression of the protooncogene SPHK1 (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #25733 \n\nLong non-coding RNA KHPS1 drives a regulatory cascade which activates expression of the protooncogene SPHK1\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .