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Elife. 2018 May 29;7. pii: e37084. doi: 10.7554/eLife.37084.

FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment.

Author information

1
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
2
Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
3
Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
4
Nuffield Department of Medicine, TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United Kingdom.
5
CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
#
Contributed equally

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.

KEYWORDS:

CDK-Mediator; CpG islands; ZF-CxxC; chromatin; chromosomes; developmental biology; gene expression; lineage commitment; mouse; stem cells; transcription

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