Toggle involving cis-interfering noncoding RNAs controls variegated gene expression in yeast

被引:154
作者
Bumgarner, Stacie L. [2 ]
Dowell, Robin D. [1 ]
Grisafi, Paula [2 ]
Gifford, David K. [1 ]
Fink, Gerald R. [2 ]
机构
[1] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA
[2] 9 Cambridge Ctr, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
基金
美国国家卫生研究院;
关键词
FLO11; intergenic transcription; Rpd3L histone deacetylase; transcriptional interference; regulatory RNAs; RPD3 HISTONE DEACETYLASE; SACCHAROMYCES-CEREVISIAE; X-CHROMOSOME; BIDIRECTIONAL PROMOTERS; ANTISENSE TRANSCRIPTION; GLOBAL IDENTIFICATION; BUDDING YEAST; KINASE; UME6; STABILIZATION;
D O I
10.1073/pnas.0909641106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The identification of specific functional roles for the numerous long noncoding (nc)RNAs found in eukaryotic transcriptomes is currently a matter of intense study amid speculation that these ncRNAs have key regulatory roles. We have identified a pair of cis-interfering ncRNAs in yeast that contribute to the control of variegated gene expression at the FLO11 locus by implementing a regulatory circuit that toggles between two stable states. These capped, polyadenylated ncRNAs are transcribed across the large intergenic region upstream of the FLO11 ORF. As with mammalian long intervening (ii)ncRNAs, these yeast ncRNAs (ICR1 and PWR1) are themselves regulated by transcription factors (Sfl1 and Flo8) and chromatin remodelers (Rpd3L) that are key elements in phenotypic transitions in yeast. The mechanism that we describe explains the unanticipated role of a histone deacetylase complex in activating gene expression, because Rpd3L mutants force the ncRNA circuit into a state that silences the expression of the adjacent variegating gene.
引用
收藏
页码:18321 / 18326
页数:6
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