Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response
Dynamic regulation of gene expression via signal transduction pathways is of fundamental importance during many biological processes such as cell state transitioning, cell cycle progression and stress responses. In this study we used serum stimulation as a cell response paradigm to apply the nascent...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2016-06-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/5/6/837 |
| _version_ | 1818671178176266240 |
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| author | Killeen S. Kirkconnell Michelle T. Paulsen Brian Magnuson Karan Bedi Mats Ljungman |
| author_facet | Killeen S. Kirkconnell Michelle T. Paulsen Brian Magnuson Karan Bedi Mats Ljungman |
| author_sort | Killeen S. Kirkconnell |
| collection | DOAJ |
| description | Dynamic regulation of gene expression via signal transduction pathways is of fundamental importance during many biological processes such as cell state transitioning, cell cycle progression and stress responses. In this study we used serum stimulation as a cell response paradigm to apply the nascent RNA Bru-seq technique in order to capture early dynamic changes in the nascent transcriptome. Our data provides an unprecedented view of the dynamics of genome-wide transcription during the first two hours of serum stimulation in human fibroblasts. While some genes showed sustained induction or repression, other genes showed transient or delayed responses. Surprisingly, the dynamic patterns of induction and suppression of response genes showed a high degree of similarity, suggesting that these opposite outcomes are triggered by a common set of signals. As expected, early response genes such as those encoding components of the AP-1 transcription factor and those involved in the circadian clock were immediately but transiently induced. Surprisingly, transcription of important DNA damage response genes and histone genes were rapidly repressed. We also show that RNA polymerase II accelerates as it transcribes large genes and this was independent of whether the gene was induced or not. These results provide a unique genome-wide depiction of dynamic patterns of transcription of serum response genes and demonstrate the utility of Bru-seq to comprehensively capture rapid and dynamic changes of the nascent transcriptome. |
| first_indexed | 2024-12-17T07:19:52Z |
| format | Article |
| id | doaj.art-0fabf321d1524c278e5f6b31df1a8259 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T07:19:52Z |
| publishDate | 2016-06-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-0fabf321d1524c278e5f6b31df1a82592022-12-21T21:58:47ZengThe Company of BiologistsBiology Open2046-63902016-06-015683784710.1242/bio.019323019323Capturing the dynamic nascent transcriptome during acute cellular responses: The serum responseKilleen S. Kirkconnell0Michelle T. Paulsen1Brian Magnuson2Karan Bedi3Mats Ljungman4 Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, and Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, and Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, and Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, and Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, and Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA Dynamic regulation of gene expression via signal transduction pathways is of fundamental importance during many biological processes such as cell state transitioning, cell cycle progression and stress responses. In this study we used serum stimulation as a cell response paradigm to apply the nascent RNA Bru-seq technique in order to capture early dynamic changes in the nascent transcriptome. Our data provides an unprecedented view of the dynamics of genome-wide transcription during the first two hours of serum stimulation in human fibroblasts. While some genes showed sustained induction or repression, other genes showed transient or delayed responses. Surprisingly, the dynamic patterns of induction and suppression of response genes showed a high degree of similarity, suggesting that these opposite outcomes are triggered by a common set of signals. As expected, early response genes such as those encoding components of the AP-1 transcription factor and those involved in the circadian clock were immediately but transiently induced. Surprisingly, transcription of important DNA damage response genes and histone genes were rapidly repressed. We also show that RNA polymerase II accelerates as it transcribes large genes and this was independent of whether the gene was induced or not. These results provide a unique genome-wide depiction of dynamic patterns of transcription of serum response genes and demonstrate the utility of Bru-seq to comprehensively capture rapid and dynamic changes of the nascent transcriptome.http://bio.biologists.org/content/5/6/837Regulation of transcriptionTranscription elongationSignal transductionGene length |
| spellingShingle | Killeen S. Kirkconnell Michelle T. Paulsen Brian Magnuson Karan Bedi Mats Ljungman Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response Biology Open Regulation of transcription Transcription elongation Signal transduction Gene length |
| title | Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response |
| title_full | Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response |
| title_fullStr | Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response |
| title_full_unstemmed | Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response |
| title_short | Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response |
| title_sort | capturing the dynamic nascent transcriptome during acute cellular responses the serum response |
| topic | Regulation of transcription Transcription elongation Signal transduction Gene length |
| url | http://bio.biologists.org/content/5/6/837 |
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