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Functional dissection of the enhancer repertoire in human embryonic stem cells

Tahsin Stefan Barakat, View ORCID ProfileFlorian Halbritter, Man Zhang, View ORCID ProfileAndré F. Rendeiro, View ORCID ProfileChristoph Bock, View ORCID ProfileIan Chambers
doi: https://doi.org/10.1101/146696
Tahsin Stefan Barakat
1MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom
5Co-first authors
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  • For correspondence: stefan.barakat@ed.ac.uk i.chambers@ed.ac.uk
Florian Halbritter
2CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria
5Co-first authors
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Man Zhang
1MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom
6Co-second authors
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André F. Rendeiro
2CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria
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Christoph Bock
2CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria
3Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
4Max Planck Institute for Informatics, Saarland Informatics Campus, 66123 Saarbrücken, Germany
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Ian Chambers
1MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom
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  • For correspondence: stefan.barakat@ed.ac.uk i.chambers@ed.ac.uk
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Summary

Enhancers are genetic elements that regulate spatiotemporal gene expression. Enhancer function requires transcription factor (TF) binding and correlates with histone modifications. However, the extent to which TF binding and histone modifications can functionally define active enhancers remains unclear. Here we combine chromatin immunoprecipitation with a massively parallel reporter assay to identify functional enhancers in human embryonic stem cells (hESCs) genome-wide in a quantitative unbiased manner. While active enhancers associate with TFs, only a minority of regions marked by NANOG, OCT4, H3K27ac and H3K4me1 function as enhancers, with activity changing markedly with culture conditions. Our analysis also reveals a novel enhancer set associated with housekeeping genes. Moreover, while transposable elements associate with putative enhancers only some exhibit activity. Similarly, within super-enhancers, large tracts are non-functional, with activity restricted to small sub-domains. This catalogue of validated enhancers provides a valuable resource for further functional dissection of the regulatory genome.

Highlights

  • A catalog of functional enhancers in hESCs including a novel housekeeping class

  • Active enhancers feature specific transcription factors and transposable elements

  • Major shifts in enhancer activity occur during induction of naive pluripotency

  • Super-enhancers consist of small units with enhancer function

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 04, 2017.
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Functional dissection of the enhancer repertoire in human embryonic stem cells
Tahsin Stefan Barakat, Florian Halbritter, Man Zhang, André F. Rendeiro, Christoph Bock, Ian Chambers
bioRxiv 146696; doi: https://doi.org/10.1101/146696
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Functional dissection of the enhancer repertoire in human embryonic stem cells
Tahsin Stefan Barakat, Florian Halbritter, Man Zhang, André F. Rendeiro, Christoph Bock, Ian Chambers
bioRxiv 146696; doi: https://doi.org/10.1101/146696

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