FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
- University of Oxford, United Kingdom
- RIKEN Center for Integrative Medical Sciences, Japan
- Kazusa DNA Research Institute, Japan
Abstract
CpG islands are gene regulatory elements associated with the majority of mammalian promoters, yet how they regulate gene expression remains poorly understood. Here, we identify FBXL19 as a CpG island-binding protein in mouse embryonic stem (ES) cells and show that it associates with the CDK-Mediator complex. We discover that FBXL19 recruits CDK-Mediator to CpG island-associated promoters of non-transcribed developmental genes to prime these genes for activation during cell lineage commitment. We further show that recognition of CpG islands by FBXL19 is essential for mouse development. Together this reveals a new CpG island-centric mechanism for CDK-Mediator recruitment to developmental gene promoters in ES cells and a requirement for CDK-Mediator in priming these developmental genes for activation during cell lineage commitment.
Data availability
Sequencing data generated in this study have been deposited in GEO under accession code GSE98756
Article and author information
Author details
Funding
Wellcome (098024/Z/11/Z)
- Robert J Klose
European Research Council (681440)
- Robert J Klose
Lister Institute of Preventive Medicine
- Robert J Klose
Japan Agency for Medical Research and Development
- Haruhiko Koseki
Sir Henry Wellcome Postdoctoral Fellowship (110286/Z/15/Z)
- Angelika Feldmann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joaquín M Espinosa, University of Colorado School of Medicine, United States
Publication history
- Received: March 29, 2018
- Accepted: May 26, 2018
- Accepted Manuscript published: May 29, 2018 (version 1)
- Version of Record published: June 12, 2018 (version 2)
Copyright
© 2018, Dimitrova et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
eLife 7:e37084.
https://doi.org/10.7554/eLife.37084
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