Enhancers predominantly regulate gene expression during differentiation via transcription initiation
| Autor: | Martin S.C. Larke, Douglas R. Higgs, Ron Schwessinger, Bryony Graham, Julia Truch, Takayuki Nojima, Robert A. Beagrie, Jelena Telenius, Damien J. Downes, Jim R. Hughes, M. A. Bender, A. Marieke Oudelaar, Nick J. Proudfoot |
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| Rok vydání: | 2021 |
| Předmět: |
Gene Expression
RNA polymerase II Context (language use) beta-Globins Article Proto-Oncogene Proteins c-myc Mice 03 medical and health sciences Fetus 0302 clinical medicine alpha-Globins Transcription (biology) Gene expression Genetics Animals Humans HSP70 Heat-Shock Proteins Promoter Regions Genetic Enhancer Molecular Biology Transcription Initiation Genetic Genetics (clinical) Gene Library 030304 developmental biology Mice Knockout Regulation of gene expression 0303 health sciences biology Effector Cell Differentiation Exons Cell Biology Introns Cell biology Enhancer Elements Genetic Genetic Techniques Gene Expression Regulation Liver Genetically Engineered Mouse biology.protein RNA Polymerase II K562 Cells 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Mol Cell |
| ISSN: | 1097-2765 |
| Popis: | 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 do transcriptional enhancers influence these events to control gene expression? Here we present an approach, which 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. |
| Databáze: | OpenAIRE |
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