CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation.

Varun Narendra, Pedro P. Rocha, Disi An, Ramya Raviram, Jane A. Skok, Esteban O. Mazzoni, Danny Reinberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1017-1021.
Number of pages5
JournalScience
Volume347
Issue number6225
DOIs
StatePublished - Feb 27 2015

Fingerprint

Chromatin
Polycomb-Group Proteins
Euchromatin
Heterochromatin
Homeobox Genes
Motor Neurons
Embryonic Stem Cells
Epigenomics
Transcriptional Activation
Cell Differentiation
Binding Sites
CCCTC-binding factor

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Narendra, V., Rocha, P. P., An, D., Raviram, R., Skok, J. A., Mazzoni, E. O., & Reinberg, D. (2015). CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. Science, 347(6225), 1017-1021.. https://doi.org/10.1126/science.1262088

CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. / Narendra, Varun; Rocha, Pedro P.; An, Disi; Raviram, Ramya; Skok, Jane A.; Mazzoni, Esteban O.; Reinberg, Danny.

In: Science, Vol. 347, No. 6225, 27.02.2015, p. 1017-1021.

Research output: Contribution to journalArticle

Narendra, V, Rocha, PP, An, D, Raviram, R, Skok, JA, Mazzoni, EO & Reinberg, D 2015, 'CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation.', Science, vol. 347, no. 6225, pp. 1017-1021.. https://doi.org/10.1126/science.1262088
Narendra, Varun ; Rocha, Pedro P. ; An, Disi ; Raviram, Ramya ; Skok, Jane A. ; Mazzoni, Esteban O. ; Reinberg, Danny. / CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. In: Science. 2015 ; Vol. 347, No. 6225. pp. 1017-1021.
@article{0539991491324bdeb38947a90a9e2b2f,
title = "CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation.",
abstract = "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.",
author = "Varun Narendra and Rocha, {Pedro P.} and Disi An and Ramya Raviram and Skok, {Jane A.} and Mazzoni, {Esteban O.} and Danny Reinberg",
year = "2015",
month = "2",
day = "27",
doi = "10.1126/science.1262088",
language = "English (US)",
volume = "347",
pages = "1017--1021.",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6225",

}

TY - JOUR

T1 - CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation.

AU - Narendra, Varun

AU - Rocha, Pedro P.

AU - An, Disi

AU - Raviram, Ramya

AU - Skok, Jane A.

AU - Mazzoni, Esteban O.

AU - Reinberg, Danny

PY - 2015/2/27

Y1 - 2015/2/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923771297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923771297&partnerID=8YFLogxK

U2 - 10.1126/science.1262088

DO - 10.1126/science.1262088

M3 - Article

C2 - 25722416

AN - SCOPUS:84923771297

VL - 347

SP - 1017-1021.

JO - Science

JF - Science

SN - 0036-8075

IS - 6225

ER -