| Title: | Disruption of promoter memory by synthesis of a long noncoding RNA |
| Author(s): | Yu Y; Yarrington RM; Chuong EB; Elde NC; Stillman DJ; |
| Address: | "Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84112; Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, UT 84112. Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84112; david.stillman@path.utah.edu" |
| ISSN/ISBN: | 1091-6490 (Electronic) 0027-8424 (Print) 0027-8424 (Linking) |
| Abstract: | "The yeast HO endonuclease is expressed in late G1 in haploid mother cells to initiate mating-type interconversion. Cells can be arrested in G1 by nutrient deprivation or by pheromone exposure, but cells that resume cycling after nutrient deprivation or cyclin-dependent kinase (CDK) inactivation express HO in the first cell cycle, whereas HO is not expressed until the second cycle after release from pheromone arrest. Here, we show that transcription of a long noncoding RNA (lncRNA) mediates this differential response. The SBF and Mediator factors remain bound to the inactive promoter during arrest due to CDK inactivation, and these bound factors allow the cell to remember a transcriptional decision made before arrest. If the presence of mating pheromone indicates that this decision is no longer appropriate, a lncRNA originating at -2700 upstream of the HO gene is induced, and the transcription machinery displaces promoter-bound SBF, preventing HO transcription in the subsequent cell cycle. Further, we find that the displaced SBF is blocked from rebinding due to incorporation of its recognition sites within nucleosomes. Expressing the pHO-lncRNA in trans is ineffective, indicating that transcription in cis is required. Factor displacement during lncRNA transcription could be a general mechanism for regulating memory of previous events at promoters" |
| Keywords: | "Base Sequence Binding Sites Endonucleases/*genetics/metabolism G1 Phase Cell Cycle Checkpoints *Gene Expression Regulation, Fungal Mediator Complex/genetics/metabolism Nucleosomes/genetics/metabolism *Promoter Regions, Genetic Protein Binding RNA, Fungal/;" |
| Notes: | "MedlineYu, Yaxin Yarrington, Robert M Chuong, Edward B Elde, Nels C Stillman, David J eng R01 GM039067/GM/NIGMS NIH HHS/ R01 GM114514/GM/NIGMS NIH HHS/ T32 DK007115/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2016/08/11 Proc Natl Acad Sci U S A. 2016 Aug 23; 113(34):9575-80. doi: 10.1073/pnas.1601793113. Epub 2016 Aug 9" |
