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10.1093/nar/gkw113

http://scihub22266oqcxt.onion/10.1093/nar/gkw113
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suck abstract from ncbi


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pmid26945044
      Nucleic+Acids+Res 2016 ; 44 (11 ): 5105-22
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  • Bidirectional promoters link cAMP signaling with irreversible differentiation through promoter-associated non-coding RNA (pancRNA) expression in PC12 cells #MMPMID26945044
  • Yamamoto N ; Agata K ; Nakashima K ; Imamura T
  • Nucleic Acids Res 2016[Jun]; 44 (11 ): 5105-22 PMID26945044 show ga
  • Bidirectional promoters are the major source of gene activation-associated noncoding RNA (ncRNA). PC12 cells offer an interesting model for understanding the mechanism underlying bidirectional promoter-mediated cell cycle control. Nerve growth factor (NGF)-stimulated PC12 cells elongate neurites, and are in a reversible cell-cycle-arrested state. In contrast, these cells irreversibly differentiate and cannot re-enter the normal cell cycle after NGF plus cAMP treatment. In this study, using directional RNA-seq, we found that bidirectional promoters for protein-coding genes with promoter-associated ncRNA (pancRNA) were enriched for cAMP response element consensus sequences, and were preferred targets for transcriptional regulation by the transcription factors in the cAMP-dependent pathway. A spindle-formation-associated gene, Nusap1 and pancNusap1 were among the most strictly co-transcribed pancRNA-mRNA pairs. This pancRNA-mRNA pair was specifically repressed in irreversibly differentiated PC12 cells. Knockdown (KD) and overexpression experiments showed that pancNusap1 positively regulated the Nusap1 expression in a sequence-specific manner, which was accompanied by histone acetylation at the Nusap1 promoter. Furthermore, pancNusap1 KD recapitulated the effects of cAMP on cell cycle arrest. Thus, we conclude that pancRNA-mediated histone acetylation contributes to the establishment of the cAMP-induced transcription state of the Nusap1 locus and contributes to the irreversible cell cycle exit for terminal differentiation of PC12 cells.
  • |*Cell Differentiation [MESH]
  • |*Gene Expression Regulation [MESH]
  • |*Promoter Regions, Genetic [MESH]
  • |*RNA, Untranslated [MESH]
  • |*Signal Transduction [MESH]
  • |Acetylation [MESH]
  • |Animals [MESH]
  • |Binding Sites [MESH]
  • |Cell Cycle Checkpoints/genetics [MESH]
  • |Cell Line [MESH]
  • |Cyclic AMP Response Element-Binding Protein/metabolism [MESH]
  • |Cyclic AMP/*metabolism [MESH]
  • |Gene Knockdown Techniques [MESH]
  • |Histones/metabolism [MESH]
  • |Humans [MESH]
  • |Nerve Growth Factor/metabolism [MESH]
  • |PC12 Cells [MESH]
  • |Protein Binding [MESH]
  • |RNA, Messenger/genetics/metabolism [MESH]
  • |Rats [MESH]
  • |Response Elements [MESH]


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