title: Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF.
abstract: CTCF is a master regulator that plays important roles in genome architecture and gene expression. How CTCF is recruited in a locus-specific manner is not fully understood. Evidence from epigenetic processes, such as X chromosome inactivation (XCI), indicates that CTCF associates functionally with RNA. Using genome-wide approaches to investigate the relationship between its RNA interactome and epigenomic landscape, here we report that CTCF binds thousands of transcripts in mouse embryonic stem cells, many in close proximity to CTCF's genomic binding sites. CTCF is a specific and high-affinity RNA-binding protein (Kd < 1 nM). During XCI, CTCF differentially binds the active and inactive X chromosomes and interacts directly with Tsix, Xite, and Xist RNAs. Tsix and Xite RNAs target CTCF to the X inactivation center, thereby inducing homologous X chromosome pairing. Our work elucidates one mechanism by which CTCF is recruited in a locus-specific manner and implicates CTCF-RNA interactions in long-range chromosomal interactions.
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Johnny T
authors.initials: JT
authors.lastname: Kung
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Kesner
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Jee Young
authors.initials: JY
authors.lastname: An
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 USA.
authors.forename: Janice Y
authors.initials: JY
authors.lastname: Ahn
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cifuentes-Rojas
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: David
authors.initials: D
authors.lastname: Colognori
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Yesu
authors.initials: Y
authors.lastname: Jeon
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Attila
authors.initials: A
authors.lastname: Szanto
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: del Rosario
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Pinter
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Erwin
authors.affiliation: Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114 USA; Department of Genetics, Harvard Medical School, Boston, MA 02115 USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 USA. Electronic address: lee@molbio.mgh.harvard.edu.
authors.forename: Jeannie T
authors.initials: JT
authors.lastname: Lee
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002478:Cells, Cultured; D023902:Chromosome Pairing; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D051379:Mice; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics*
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins