Genetic dissection of the RNA polymerase II transcription cycle
How DNA sequence affects the dynamics and position of RNA Polymerase II (Pol II) during transcription remains poorly understood. Here, we used naturally occurring genetic variation in F1 hybrid mice to explore how DNA sequence differences affect the genome-wide distribution of Pol II. We measured th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/78458 |
| _version_ | 1818018312089501696 |
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| author | Shao-Pei Chou Adriana K Alexander Edward J Rice Lauren A Choate Charles G Danko |
| author_facet | Shao-Pei Chou Adriana K Alexander Edward J Rice Lauren A Choate Charles G Danko |
| author_sort | Shao-Pei Chou |
| collection | DOAJ |
| description | How DNA sequence affects the dynamics and position of RNA Polymerase II (Pol II) during transcription remains poorly understood. Here, we used naturally occurring genetic variation in F1 hybrid mice to explore how DNA sequence differences affect the genome-wide distribution of Pol II. We measured the position and orientation of Pol II in eight organs collected from heterozygous F1 hybrid mice using ChRO-seq. Our data revealed a strong genetic basis for the precise coordinates of transcription initiation and promoter proximal pause, allowing us to redefine molecular models of core transcriptional processes. Our results implicate DNA sequence, including both known and novel DNA sequence motifs, as key determinants of the position of Pol II initiation and pause. We report evidence that initiation site selection follows a stochastic process similar to Brownian motion along the DNA template. We found widespread differences in the position of transcription termination, which impact the primary structure and stability of mature mRNA. Finally, we report evidence that allelic changes in transcription often affect mRNA and ncRNA expression across broad genomic domains. Collectively, we reveal how DNA sequences shape core transcriptional processes at single nucleotide resolution in mammals. |
| first_indexed | 2024-04-14T07:37:18Z |
| format | Article |
| id | doaj.art-0d48e7764b8b4123ab81d53bbb14c3e0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:37:18Z |
| publishDate | 2022-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0d48e7764b8b4123ab81d53bbb14c3e02022-12-22T02:05:38ZengeLife Sciences Publications LtdeLife2050-084X2022-07-011110.7554/eLife.78458Genetic dissection of the RNA polymerase II transcription cycleShao-Pei Chou0Adriana K Alexander1Edward J Rice2Lauren A Choate3https://orcid.org/0000-0003-4246-0550Charles G Danko4https://orcid.org/0000-0002-1999-7125Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, United StatesBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, United States; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, United StatesBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, United StatesBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, United StatesBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, United States; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, United StatesHow DNA sequence affects the dynamics and position of RNA Polymerase II (Pol II) during transcription remains poorly understood. Here, we used naturally occurring genetic variation in F1 hybrid mice to explore how DNA sequence differences affect the genome-wide distribution of Pol II. We measured the position and orientation of Pol II in eight organs collected from heterozygous F1 hybrid mice using ChRO-seq. Our data revealed a strong genetic basis for the precise coordinates of transcription initiation and promoter proximal pause, allowing us to redefine molecular models of core transcriptional processes. Our results implicate DNA sequence, including both known and novel DNA sequence motifs, as key determinants of the position of Pol II initiation and pause. We report evidence that initiation site selection follows a stochastic process similar to Brownian motion along the DNA template. We found widespread differences in the position of transcription termination, which impact the primary structure and stability of mature mRNA. Finally, we report evidence that allelic changes in transcription often affect mRNA and ncRNA expression across broad genomic domains. Collectively, we reveal how DNA sequences shape core transcriptional processes at single nucleotide resolution in mammals.https://elifesciences.org/articles/78458RNA polymerase IItranscriptiongene expression |
| spellingShingle | Shao-Pei Chou Adriana K Alexander Edward J Rice Lauren A Choate Charles G Danko Genetic dissection of the RNA polymerase II transcription cycle eLife RNA polymerase II transcription gene expression |
| title | Genetic dissection of the RNA polymerase II transcription cycle |
| title_full | Genetic dissection of the RNA polymerase II transcription cycle |
| title_fullStr | Genetic dissection of the RNA polymerase II transcription cycle |
| title_full_unstemmed | Genetic dissection of the RNA polymerase II transcription cycle |
| title_short | Genetic dissection of the RNA polymerase II transcription cycle |
| title_sort | genetic dissection of the rna polymerase ii transcription cycle |
| topic | RNA polymerase II transcription gene expression |
| url | https://elifesciences.org/articles/78458 |
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