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  Enhancers predominantly regulate gene expression during differentiation via transcription initiation

Larke, M. S. C., Schwessinger, R., Nojima, T., Telenius, J., Beagrie, R. A., Downes, D. J., et al. (2021). Enhancers predominantly regulate gene expression during differentiation via transcription initiation. Molecular Cell, 81(5), 983-997.e7. doi:10.1016/j.molcel.2021.01.002.

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Genre: Journal Article

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 Creators:
Larke, M. S. C., Author
Schwessinger, R., Author
Nojima, T., Author
Telenius, J., Author
Beagrie, R. A., Author
Downes, D. J., Author
Oudelaar, A. M.1, Author           
Truch, J., Author
Graham, B., Author
Bender, M. A., Author
Proudfoot, N. J., Author
Higgs, D. R., Author
Hughes, J. R., Author
Affiliations:
1Lise Meitner Group Genome Organization and Regulation, MPI for Biophysical Chemistry, Max Planck Society, ou_3261271              

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Free keywords: gene regulation; enhancers; transcription; promoter proximal pausing; Poll II recruitment
 Abstract: 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.

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Language(s): eng - English
 Dates: 2021-02-032021-03-04
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2021.01.002
 Degree: -

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Title: Molecular Cell
Source Genre: Journal
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Pages: - Volume / Issue: 81 (5) Sequence Number: - Start / End Page: 983 - 997.e7 Identifier: -