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

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...

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Main Authors:	Emilia Dimitrova, Takashi Kondo, Angelika Feldmann, Manabu Nakayama, Yoko Koseki, Rebecca Konietzny, Benedikt M Kessler, Haruhiko Koseki, Robert J Klose
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2018-05-01
Series:	eLife
Subjects:	chromatin CpG islands CDK-Mediator ZF-CxxC transcription lineage commitment
Online Access:	https://elifesciences.org/articles/37084

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spelling	doaj-e1ac4beed4eb453a8c6554167bc7f70f2021-05-05T15:52:58ZengeLife Sciences Publications LtdeLife2050-084X2018-05-01710.7554/eLife.37084FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitmentEmilia Dimitrova0https://orcid.org/0000-0001-5669-1240Takashi Kondo1Angelika Feldmann2Manabu Nakayama3Yoko Koseki4Rebecca Konietzny5Benedikt M Kessler6Haruhiko Koseki7https://orcid.org/0000-0001-8424-5854Robert J Klose8https://orcid.org/0000-0002-8726-7888Department of Biochemistry, University of Oxford, Oxford, United KingdomLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Technology Development, Kazusa DNA Research Institute, Kisarazu, JapanLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, JapanNuffield Department of Medicine, TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United KingdomNuffield Department of Medicine, TDI Mass Spectrometry Laboratory, Target Discovery Institute, University of Oxford, Oxford, United KingdomLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, JapanDepartment of Biochemistry, University of Oxford, Oxford, United KingdomCpG 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.https://elifesciences.org/articles/37084chromatinCpG islandsCDK-MediatorZF-CxxCtranscriptionlineage commitment
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Emilia Dimitrova Takashi Kondo Angelika Feldmann Manabu Nakayama Yoko Koseki Rebecca Konietzny Benedikt M Kessler Haruhiko Koseki Robert J Klose
spellingShingle	Emilia Dimitrova Takashi Kondo Angelika Feldmann Manabu Nakayama Yoko Koseki Rebecca Konietzny Benedikt M Kessler Haruhiko Koseki Robert J Klose FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment eLife chromatin CpG islands CDK-Mediator ZF-CxxC transcription lineage commitment
author_facet	Emilia Dimitrova Takashi Kondo Angelika Feldmann Manabu Nakayama Yoko Koseki Rebecca Konietzny Benedikt M Kessler Haruhiko Koseki Robert J Klose
author_sort	Emilia Dimitrova
title	FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
title_short	FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
title_full	FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
title_fullStr	FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
title_full_unstemmed	FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment
title_sort	fbxl19 recruits cdk-mediator to cpg islands of developmental genes priming them for activation during lineage commitment
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2018-05-01
description	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.
topic	chromatin CpG islands CDK-Mediator ZF-CxxC transcription lineage commitment
url	https://elifesciences.org/articles/37084
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FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment

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