CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation.
Polycomb and Trithorax group proteins encode the epigenetic memory of cellular positional identity by establishing inheritable domains of repressive and active chromatin within the Hox clusters. Here we demonstrate that the CCCTC-binding factor (CTCF) functions to insulate these adjacent yet antagonistic chromatin domains during embryonic stem cell differentiation into cervical motor neurons. Deletion of CTCF binding sites within the Hox clusters results in the expansion of active chromatin into the repressive domain. CTCF functions as an insulator by organizing Hox clusters into spatially disjoint domains. Ablation of CTCF binding disrupts topological boundaries such that caudal Hox genes leave the repressed domain and become subject to transcriptional activation. Hence, CTCF is required to insulate facultative heterochromatin from impinging euchromatin to produce discrete positional identities.
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA.
Varun
V
Narendra
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Pedro P
PP
Rocha
Department of Biology, New York University, New York, NY 10003, USA.
Disi
D
An
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Ramya
R
Raviram
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Jane A
JA
Skok
Department of Biology, New York University, New York, NY 10003, USA. danny.reinberg@nyumc.org eom204@nyu.edu.
Esteban O
EO
Mazzoni
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA. danny.reinberg@nyumc.org eom204@nyu.edu.
Danny
D
Reinberg
D000818:Animals; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation / Q000235:genetics*; D002843:Chromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D053595:Embryonic Stem Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000166:cytology*; D005810:Multigene Family; D009333:Neck; D017434:Protein Structure, Tertiary; D051381:Rats; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D012097:Repressor Proteins