Enhancers predominantly regulate gene expression during differentiation via transcription initiation
Gene transcription occurs via a cycle of linked events, including initiation, promoter-proximal pausing, and elongation of RNA polymerase II (Pol II). A key question is how transcriptional enhancers influence these events to control gene expression. Here, we present an approach that evaluates the le...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2021
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| _version_ | 1826261535546146816 |
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| author | Larke, MSC Schwessinger, R Nojima, T Telenius, J Beagrie, RA Downes, DJ Oudelaar, AM Truch, J Graham, B Bender, MA Proudfoot, NJ Higgs, DR Hughes, JR |
| author_facet | Larke, MSC Schwessinger, R Nojima, T Telenius, J Beagrie, RA Downes, DJ Oudelaar, AM Truch, J Graham, B Bender, MA Proudfoot, NJ Higgs, DR Hughes, JR |
| author_sort | Larke, MSC |
| collection | OXFORD |
| description | Gene transcription occurs via a cycle of linked events, including initiation, promoter-proximal pausing, and elongation of RNA polymerase II (Pol II). A key question is how transcriptional enhancers influence these events to control gene expression. Here, we present an approach that evaluates the level and change in promoter-proximal transcription (initiation and pausing) in the context of differential gene expression, genome-wide. This combinatorial approach shows that in primary cells, control of gene expression during differentiation is achieved predominantly via changes in transcription initiation rather than via release of Pol II pausing. Using genetically engineered mouse models, deleted for functionally validated enhancers of the α- and β-globin loci, we confirm that these elements regulate Pol II recruitment and/or initiation to modulate gene expression. Together, our data show that gene expression during differentiation is regulated predominantly at the level of initiation and that enhancers are key effectors of this process. |
| first_indexed | 2024-03-06T19:22:53Z |
| format | Journal article |
| id | oxford-uuid:1ab3ab82-8d6c-4e28-840d-734933e0b263 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:22:53Z |
| publishDate | 2021 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:1ab3ab82-8d6c-4e28-840d-734933e0b2632022-03-26T10:56:19ZEnhancers predominantly regulate gene expression during differentiation via transcription initiationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1ab3ab82-8d6c-4e28-840d-734933e0b263EnglishSymplectic ElementsCell Press2021Larke, MSCSchwessinger, RNojima, TTelenius, JBeagrie, RADownes, DJOudelaar, AMTruch, JGraham, BBender, MAProudfoot, NJHiggs, DRHughes, JRGene transcription occurs via a cycle of linked events, including initiation, promoter-proximal pausing, and elongation of RNA polymerase II (Pol II). A key question is how transcriptional enhancers influence these events to control gene expression. Here, we present an approach that evaluates the level and change in promoter-proximal transcription (initiation and pausing) in the context of differential gene expression, genome-wide. This combinatorial approach shows that in primary cells, control of gene expression during differentiation is achieved predominantly via changes in transcription initiation rather than via release of Pol II pausing. Using genetically engineered mouse models, deleted for functionally validated enhancers of the α- and β-globin loci, we confirm that these elements regulate Pol II recruitment and/or initiation to modulate gene expression. Together, our data show that gene expression during differentiation is regulated predominantly at the level of initiation and that enhancers are key effectors of this process. |
| spellingShingle | Larke, MSC Schwessinger, R Nojima, T Telenius, J Beagrie, RA Downes, DJ Oudelaar, AM Truch, J Graham, B Bender, MA Proudfoot, NJ Higgs, DR Hughes, JR Enhancers predominantly regulate gene expression during differentiation via transcription initiation |
| title | Enhancers predominantly regulate gene expression during differentiation via transcription initiation |
| title_full | Enhancers predominantly regulate gene expression during differentiation via transcription initiation |
| title_fullStr | Enhancers predominantly regulate gene expression during differentiation via transcription initiation |
| title_full_unstemmed | Enhancers predominantly regulate gene expression during differentiation via transcription initiation |
| title_short | Enhancers predominantly regulate gene expression during differentiation via transcription initiation |
| title_sort | enhancers predominantly regulate gene expression during differentiation via transcription initiation |
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