title: Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming.
abstract: The chromatin state of pluripotency genes has been studied extensively in embryonic stem cells (ESCs) and differentiated cells, but their potential interactions with other parts of the genome remain largely unexplored. Here, we identified a genome-wide, pluripotency-specific interaction network around the Nanog promoter by adapting circular chromosome conformation capture sequencing. This network was rearranged during differentiation and restored in induced pluripotent stem cells. A large fraction of Nanog-interacting loci were bound by Mediator or cohesin in pluripotent cells. Depletion of these proteins from ESCs resulted in a disruption of contacts and the acquisition of a differentiation-specific interaction pattern prior to obvious transcriptional and phenotypic changes. Similarly, the establishment of Nanog interactions during reprogramming often preceded transcriptional upregulation of associated genes, suggesting a causative link. Our results document a complex, pluripotency-specific chromatin "interactome" for Nanog and suggest a functional role for long-range genomic interactions in the maintenance and induction of pluripotency.
authors.affiliation: Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Effie
authors.initials: E
authors.lastname: Apostolou
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferrari
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Walsh
authors.forename: Ori
authors.initials: O
authors.lastname: Bar-Nur
authors.forename: Matthias
authors.initials: M
authors.lastname: Stadtfeld
authors.forename: Sihem
authors.initials: S
authors.lastname: Cheloufi
authors.forename: Hannah T
authors.initials: HT
authors.lastname: Stuart
authors.forename: Jose M
authors.initials: JM
authors.lastname: Polo
authors.forename: Toshiro K
authors.initials: TK
authors.lastname: Ohsumi
authors.forename: Mark L
authors.initials: ML
authors.lastname: Borowsky
authors.forename: Peter V
authors.initials: PV
authors.lastname: Kharchenko
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Park
authors.forename: Konrad
authors.initials: K
authors.lastname: Hochedlinger
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics*; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D016678:Genome / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D000071317:Nanog Homeobox Protein; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse