title: A dynamic CTCF chromatin binding landscape promotes DNA hydroxymethylation and transcriptional induction of adipocyte differentiation.
abstract: CCCTC-binding factor (CTCF) is a ubiquitously expressed multifunctional transcription factor characterized by chromatin binding patterns often described as largely invariant. In this context, how CTCF chromatin recruitment and functionalities are used to promote cell type-specific gene expression remains poorly defined. Here, we show that, in addition to constitutively bound CTCF binding sites (CTS), the CTCF cistrome comprises a large proportion of sites showing highly dynamic binding patterns during the course of adipogenesis. Interestingly, dynamic CTCF chromatin binding is positively linked with changes in expression of genes involved in biological functions defining the different stages of adipogenesis. Importantly, a subset of these dynamic CTS are gained at cell type-specific regulatory regions, in line with a requirement for CTCF in transcriptional induction of adipocyte differentiation. This relates to, at least in part, CTCF requirement for transcriptional activation of both the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARG) and its target genes. Functionally, we show that CTCF interacts with TET methylcytosine dioxygenase (TET) enzymes and promotes adipogenic transcriptional enhancer DNA hydroxymethylation. Our study reveals a dynamic CTCF chromatin binding landscape required for epigenomic remodeling of enhancers and transcriptional activation driving cell differentiation.
authors.affiliation: Inserm UMR U1011, F-59000 Lille, France Université Lille 2, F-59000 Lille, France Institut Pasteur de Lille, F-59019 Lille, France European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Dubois-Chevalier
authors.affiliation: Inserm UMR U1011, F-59000 Lille, France Université Lille 2, F-59000 Lille, France Institut Pasteur de Lille, F-59019 Lille, France European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
authors.forename: Frédérik
authors.initials: F
authors.lastname: Oger
authors.affiliation: Inserm UMR U1011, F-59000 Lille, France Université Lille 2, F-59000 Lille, France Institut Pasteur de Lille, F-59019 Lille, France European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dehondt
authors.affiliation: Inserm UMR U1011, F-59000 Lille, France Université Lille 2, F-59000 Lille, France Institut Pasteur de Lille, F-59019 Lille, France European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
authors.forename: François F
authors.initials: FF
authors.lastname: Firmin
authors.affiliation: Inserm UMR U1011, F-59000 Lille, France Université Lille 2, F-59000 Lille, France Institut Pasteur de Lille, F-59019 Lille, France European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Gheeraert
authors.affiliation: Inserm UMR U1011, F-59000 Lille, France Université Lille 2, F-59000 Lille, France Institut Pasteur de Lille, F-59019 Lille, France European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Inserm UMR U1011, F-59000 Lille, France Université Lille 2, F-59000 Lille, France Institut Pasteur de Lille, F-59019 Lille, France European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France jerome.eeckhoute@inserm.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
authors.affiliation: Inserm UMR U1011, F-59000 Lille, France Université Lille 2, F-59000 Lille, France Institut Pasteur de Lille, F-59019 Lille, France European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France jerome.eeckhoute@inserm.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Eeckhoute
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D019175:DNA Methylation; D049308:Dioxygenases / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D057809:HEK293 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D047495:PPAR gamma; D012097:Repressor Proteins; D049308:Dioxygenases