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Regions of very low H3K27me3 partition the Drosophila genome into topological domains

Sherif El-Sharnouby, Bettina Fischer, Jose Paolo Magbanua, Benjamin Umans, Rosalyn Flower, Siew Woh Choo, Steven Russell, Robert White
doi: https://doi.org/10.1101/072900
Sherif El-Sharnouby
1Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3DY United Kingdom
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Bettina Fischer
2Department of Genetics, University of Cambridge, CB2 3EH United Kingdom
3Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR United Kingdom
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Jose Paolo Magbanua
1Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3DY United Kingdom
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Benjamin Umans
1Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3DY United Kingdom
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Rosalyn Flower
1Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3DY United Kingdom
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Siew Woh Choo
4Department of Oral and Craniofacial Sciences, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
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Steven Russell
2Department of Genetics, University of Cambridge, CB2 3EH United Kingdom
3Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR United Kingdom
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Robert White
1Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3DY United Kingdom
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Abstract

Background It is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood.

Results We have investigated boundary regions in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing mid-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4/Putzig. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the transcription start sites of housekeeping genes than with the H3K27me3 domain boundaries.

Conclusions We suggest that the D domain chromatin state, characterised by very low H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome.

Footnotes

  • Sherif El-Sharnouby se266{at}cam.ac.uk

  • Bettina Fischer bef22{at}cam.ac.uk

  • Jose Paolo Magbanua jpvm{at}mac.com

  • Benjamin Umans umans{at}fas.harvard.edu

  • Rosalyn Flower rosalyn.flower{at}crick.ac.uk

  • Siew Woh Choo csw1978{at}hotmail.com

  • Steven Russell sr120{at}cam.ac.uk

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 01, 2016.
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Regions of very low H3K27me3 partition the Drosophila genome into topological domains
Sherif El-Sharnouby, Bettina Fischer, Jose Paolo Magbanua, Benjamin Umans, Rosalyn Flower, Siew Woh Choo, Steven Russell, Robert White
bioRxiv 072900; doi: https://doi.org/10.1101/072900
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Regions of very low H3K27me3 partition the Drosophila genome into topological domains
Sherif El-Sharnouby, Bettina Fischer, Jose Paolo Magbanua, Benjamin Umans, Rosalyn Flower, Siew Woh Choo, Steven Russell, Robert White
bioRxiv 072900; doi: https://doi.org/10.1101/072900

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