Transcription levels of a noncoding RNA orchestrate opposing regulatory and cell fate outcomes in yeast
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ABSTRACT:
PROVIDER: PRJNA577695 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10283200.fastq.gz | Fastqsanger.gz | |||
| SRR10283164.fastq.gz | Fastqsanger.gz | |||
| SRR10283165.fastq.gz | Fastqsanger.gz | |||
| SRR10283166.fastq.gz | Fastqsanger.gz | |||
| SRR10283167.fastq.gz | Fastqsanger.gz |
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Project description:Transcription through noncoding regions of the genome is pervasive. How these transcription events regulate gene expression remains poorly understood. Here, we report that, in S. cerevisiae, the levels of transcription through a noncoding region, IRT2, located upstream in the promoter of the inducer of meiosis, IME1, regulate opposing chromatin and transcription states. At low levels, the act of IRT2 transcription promotes histone exchange, delivering acetylated histone H3 lysine 56 to chromatin locally. The subsequent open chromatin state directs transcription factor recruitment and induces downstream transcription to repress the IME1 promoter and meiotic entry. Conversely, increasing transcription turns IRT2 into a repressor by promoting transcription-coupled chromatin assembly. The two opposing functions of IRT2 transcription shape a regulatory circuit, which ensures a robust cell-type-specific control of IME1 expression and yeast meiosis. Our data illustrate how intergenic transcription levels are key to controlling local chromatin state, gene expression, and cell fate outcomes.
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Project description:Long noncoding RNAs (lncRNA) play diverse roles in gene regulation controlling key cellular processes, most notably, cell-fate programming {Anderson, 2016 #20;Flynn, 2014 #16;Guttman, 2011 #35;Wang, 2011 #18}. Many long noncoding RNAs (lncRNAs) act in cis through transcription-coupled chromatin alterations that drive changes in local gene expression { Martens, 2004 #47; Kim, 2012 #74;van Werven, 2012 #57;Hainer, 2011 #73;Kim, 2016 #41;Ard, 2016 #21;Latos, 2012 #7}. How transcription of some lncRNAs leads to activation of gene expression, while others inhibit and repress gene expression remains poorly understood {Kornienko, 2013 #17}. Here we investigated in S. cerevisiae the function of the lncRNA IRT2, which is expressed upstream in the promoter of the master regulator for entry into meiosis, IME1. We report the surprising finding that distinct levels of IRT2 transcription regulates opposing chromatin and transcription states in order to ensure that only diploids, and not haploids, enter meiosis and form gametes. In haploid cells, IRT2 transcription at very low levels is required for the correct induction of the adjacent lncRNA IRT1, which in turn represses the IME1 promoter and prevents meiotic entry {van Werven, 2012 #57}. Low levels of IRT2 transcription stimulates histone exchange delivering acetylated histone H3 lysine 56 (H3K56ac) to chromatin, thereby facilitating chromatin disassembly and recruitment of the transcriptional activator of IRT1, Rme1. Inhibiting IRT2 transcription, or mutations that resulted in cells lacking H3K56ac impairs Rme1 recruitment and IRT1 induction, and consequently haploid cells induce IME1 and undergo a lethal meiosis. In contrast to its function at low levels, increasing IRT2 transcription enhances transcription-coupled chromatin assembly and interferes with IRT1 expression, promoting IME1 expression and meiotic entry in diploid cells {Moretto, 2018 #10}. Thus, transcription of lncRNAs, even at very low levels, can play an important role in regulating gene expression, and changes in lncRNA transcription levels can confer distinct regulatory and cell fate outcomes.
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Project description:Long noncoding RNAs (lncRNA) play diverse roles in gene regulation controlling key cellular processes, most notably, cell-fate programming {Anderson, 2016 #20;Flynn, 2014 #16;Guttman, 2011 #35;Wang, 2011 #18}. Many long noncoding RNAs (lncRNAs) act in cis through transcription-coupled chromatin alterations that drive changes in local gene expression { Martens, 2004 #47; Kim, 2012 #74;van Werven, 2012 #57;Hainer, 2011 #73;Kim, 2016 #41;Ard, 2016 #21;Latos, 2012 #7}. How transcription of some lncRNAs leads to activation of gene expression, while others inhibit and repress gene expression remains poorly understood {Kornienko, 2013 #17}. Here we investigated in S. cerevisiae the function of the lncRNA IRT2, which is expressed upstream in the promoter of the master regulator for entry into meiosis, IME1. We report the surprising finding that distinct levels of IRT2 transcription regulates opposing chromatin and transcription states in order to ensure that only diploids, and not haploids, enter meiosis and form gametes. In haploid cells, IRT2 transcription at very low levels is required for the correct induction of the adjacent lncRNA IRT1, which in turn represses the IME1 promoter and prevents meiotic entry {van Werven, 2012 #57}. Low levels of IRT2 transcription stimulates histone exchange delivering acetylated histone H3 lysine 56 (H3K56ac) to chromatin, thereby facilitating chromatin disassembly and recruitment of the transcriptional activator of IRT1, Rme1. Inhibiting IRT2 transcription, or mutations that resulted in cells lacking H3K56ac impairs Rme1 recruitment and IRT1 induction, and consequently haploid cells induce IME1 and undergo a lethal meiosis. In contrast to its function at low levels, increasing IRT2 transcription enhances transcription-coupled chromatin assembly and interferes with IRT1 expression, promoting IME1 expression and meiotic entry in diploid cells {Moretto, 2018 #10}. Thus, transcription of lncRNAs, even at very low levels, can play an important role in regulating gene expression, and changes in lncRNA transcription levels can confer distinct regulatory and cell fate outcomes.
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Project description:Long noncoding RNAs (lncRNA) play diverse roles in gene regulation controlling key cellular processes, most notably, cell-fate programming {Anderson, 2016 #20;Flynn, 2014 #16;Guttman, 2011 #35;Wang, 2011 #18}. Many long noncoding RNAs (lncRNAs) act in cis through transcription-coupled chromatin alterations that drive changes in local gene expression { Martens, 2004 #47; Kim, 2012 #74;van Werven, 2012 #57;Hainer, 2011 #73;Kim, 2016 #41;Ard, 2016 #21;Latos, 2012 #7}. How transcription of some lncRNAs leads to activation of gene expression, while others inhibit and repress gene expression remains poorly understood {Kornienko, 2013 #17}. Here we investigated in S. cerevisiae the function of the lncRNA IRT2, which is expressed upstream in the promoter of the master regulator for entry into meiosis, IME1. We report the surprising finding that distinct levels of IRT2 transcription regulates opposing chromatin and transcription states in order to ensure that only diploids, and not haploids, enter meiosis and form gametes. In haploid cells, IRT2 transcription at very low levels is required for the correct induction of the adjacent lncRNA IRT1, which in turn represses the IME1 promoter and prevents meiotic entry {van Werven, 2012 #57}. Low levels of IRT2 transcription stimulates histone exchange delivering acetylated histone H3 lysine 56 (H3K56ac) to chromatin, thereby facilitating chromatin disassembly and recruitment of the transcriptional activator of IRT1, Rme1. Inhibiting IRT2 transcription, or mutations that resulted in cells lacking H3K56ac impairs Rme1 recruitment and IRT1 induction, and consequently haploid cells induce IME1 and undergo a lethal meiosis. In contrast to its function at low levels, increasing IRT2 transcription enhances transcription-coupled chromatin assembly and interferes with IRT1 expression, promoting IME1 expression and meiotic entry in diploid cells {Moretto, 2018 #10}. Thus, transcription of lncRNAs, even at very low levels, can play an important role in regulating gene expression, and changes in lncRNA transcription levels can confer distinct regulatory and cell fate outcomes.
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