Format

Send to

Choose Destination
Mol Cell. 2015 Jan 22;57(2):361-75. doi: 10.1016/j.molcel.2014.12.006. Epub 2015 Jan 8.

Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF.

Author information

1
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.
2
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.
3
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.

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.

PMID:
25578877
PMCID:
PMC4316200
DOI:
10.1016/j.molcel.2014.12.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center