CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing
Summary: In eukaryotic genomes, heterochromatin is targeted by RNAi machinery and/or by pathways requiring RNA elimination and transcription termination factors. However, a direct connection between termination machinery and RNA polymerase II (RNAPII) transcriptional activity at heterochromatic loci...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719307545 |
| _version_ | 1818336397136756736 |
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| author | Tommy V. Vo Jothy Dhakshnamoorthy Madeline Larkin Martin Zofall Gobi Thillainadesan Vanivilasini Balachandran Sahana Holla David Wheeler Shiv I.S. Grewal |
| author_facet | Tommy V. Vo Jothy Dhakshnamoorthy Madeline Larkin Martin Zofall Gobi Thillainadesan Vanivilasini Balachandran Sahana Holla David Wheeler Shiv I.S. Grewal |
| author_sort | Tommy V. Vo |
| collection | DOAJ |
| description | Summary: In eukaryotic genomes, heterochromatin is targeted by RNAi machinery and/or by pathways requiring RNA elimination and transcription termination factors. However, a direct connection between termination machinery and RNA polymerase II (RNAPII) transcriptional activity at heterochromatic loci has remained elusive. Here, we show that, in fission yeast, the conserved cleavage and polyadenylation factor (CPF) is a key component involved in RNAi-independent assembly of constitutive and facultative heterochromatin domains and that CPF is broadly required to silence genes regulated by Clr4SUV39H. Remarkably, CPF is recruited to non-canonical termination sites within the body of genes by the YTH family RNA-binding protein Mmi1 and is required for RNAPII transcription termination and facultative heterochromatin assembly. CPF loading by Mmi1 also promotes the selective termination of long non-coding RNAs that regulate gene expression in cis. These analyses delineate a mechanism in which CPF loaded onto non-canonical termination sites specifies targets of heterochromatin assembly and gene silencing. : Vo et al. report that the YTH family RNA-binding protein Mmi1 recruits the cleavage and polyadenylation factor (CPF) to non-canonical transcription termination sites within gene bodies to promote RNA polymerase II termination and RNAi-independent heterochromatin assembly. They show that CPF is required to silence genes that are regulated by the histone methyltransferase Clr4. Keywords: facultative, heterochromatin, gene silencing, Mmi1, YTH, CPF, histone methylation, RNA polymerase II, transcription termination, pre-mRNA processing |
| first_indexed | 2024-12-13T14:38:40Z |
| format | Article |
| id | doaj.art-4e7be2568e174b8f9a71ca8f72bb14fa |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T14:38:40Z |
| publishDate | 2019-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4e7be2568e174b8f9a71ca8f72bb14fa2022-12-21T23:41:39ZengElsevierCell Reports2211-12472019-07-01281267281.e5CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene SilencingTommy V. Vo0Jothy Dhakshnamoorthy1Madeline Larkin2Martin Zofall3Gobi Thillainadesan4Vanivilasini Balachandran5Sahana Holla6David Wheeler7Shiv I.S. Grewal8Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USALaboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USALaboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USALaboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USALaboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USALaboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USALaboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USALaboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USALaboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Corresponding authorSummary: In eukaryotic genomes, heterochromatin is targeted by RNAi machinery and/or by pathways requiring RNA elimination and transcription termination factors. However, a direct connection between termination machinery and RNA polymerase II (RNAPII) transcriptional activity at heterochromatic loci has remained elusive. Here, we show that, in fission yeast, the conserved cleavage and polyadenylation factor (CPF) is a key component involved in RNAi-independent assembly of constitutive and facultative heterochromatin domains and that CPF is broadly required to silence genes regulated by Clr4SUV39H. Remarkably, CPF is recruited to non-canonical termination sites within the body of genes by the YTH family RNA-binding protein Mmi1 and is required for RNAPII transcription termination and facultative heterochromatin assembly. CPF loading by Mmi1 also promotes the selective termination of long non-coding RNAs that regulate gene expression in cis. These analyses delineate a mechanism in which CPF loaded onto non-canonical termination sites specifies targets of heterochromatin assembly and gene silencing. : Vo et al. report that the YTH family RNA-binding protein Mmi1 recruits the cleavage and polyadenylation factor (CPF) to non-canonical transcription termination sites within gene bodies to promote RNA polymerase II termination and RNAi-independent heterochromatin assembly. They show that CPF is required to silence genes that are regulated by the histone methyltransferase Clr4. Keywords: facultative, heterochromatin, gene silencing, Mmi1, YTH, CPF, histone methylation, RNA polymerase II, transcription termination, pre-mRNA processinghttp://www.sciencedirect.com/science/article/pii/S2211124719307545 |
| spellingShingle | Tommy V. Vo Jothy Dhakshnamoorthy Madeline Larkin Martin Zofall Gobi Thillainadesan Vanivilasini Balachandran Sahana Holla David Wheeler Shiv I.S. Grewal CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing Cell Reports |
| title | CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing |
| title_full | CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing |
| title_fullStr | CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing |
| title_full_unstemmed | CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing |
| title_short | CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing |
| title_sort | cpf recruitment to non canonical transcription termination sites triggers heterochromatin assembly and gene silencing |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719307545 |
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