CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation
Open accessAbstract
Keeping repressed genes repressed: Hox genes confer positional identity to cells and tissues. Maintaining precise spatial patterns of Hox gene expression is vital during metazoan development. The transcriptional repressor CTCF is involved in the regulation of chromatin architecture. Narendra et al. show that a CTCF protein binding site insulates regions of active and repressed Hox gene expression from each other. This protects heterochromatin containing repressed Hox genes from the encroaching spread of active chromatin. The CTCF protein appears to organize the active and repressed chromatin regions into distinct architectural domains. Science , this issue p. 1017
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Spatial organization of chromatin, including long-range DNA interactions, plays a key role in controlling gene expression and maintaining cellular identity.
“The spatial organization of chromatin, including a variety of long-range DNA interactions, plays a key role in controlling gene expression and maintaining cellular identity (Gorkin et al., 2014; Kundu et al., 2017; Narendra et al., 2015; Schoenfelder et al., 2015; Zirkel et al., 2018).”
From Loss of epigenetic information as a cause of mammalian aging (2023) · cites this paper as Narendra et al., 2015
Genetic perturbation of CTCF binding has been shown to result in misregulation of gene expression in various cell lines and cancer.
“While genetic perturbation of CTCF binding has been shown to result in misregulation of gene expression in various cell lines and cancer9–11,28”
From Tissue-specific CTCF-cohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo (2017) · cites this paper as [28]
Chromatin domains span >90% of the genome and are thought to create insulated neighborhoods demarcating the search space of specific long-range interactions between enhancers and their target genes.
“Such chromatin domains span >90% of the genome and are thought to create insulated neighborhoods demarcating the search space of specific long-range interactions between enhancers and their target genes (Dowen et al., 2014; Narendra et al., 2015; Symmons et al., 2014).”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Narendra et al., 2015
Dynamic loop extrusion models can explain recent perturbation experiments where CTCF binding sites have been added or deleted and also explain the loss of either CTCF or cohesin.
“Notably, a key advantage of dynamic loop extrusion models is that they can explain recent perturbation experiments where CTCF binding sites have been added or deleted9,49-51 and also explain the loss of either CTCF or cohesin.10-15”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [49]
CTCF sites located within a Hox gene cluster play a critical role in proper expression of Hox genes; some of these critical CTCF sites form insulated neighborhood anchors in ES cells.
“Positional information in the developing embryo depends on the precise expression of Homeobox (Hox) genes, and CTCF sites located within a Hox gene cluster play a critical role in proper expression of Hox genes (Narendra et al., 2015); some of these critical CTCF sites form insulated neighborhood anchors in ES cells.”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Narendra et al., 2015
CTCF binding and CTCF-CTCF loop formation can be cell type-specific.
“there is some evidence that CTCF binding and CTCF-CTCF loop formation can be cell type-specific (Narendra et al., 2015; Splinter et al., 2006; Tolhuis et al., 2002; Wang et al., 2012).”
From Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control (2016) · cites this paper as Narendra et al., 2015
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- Authors
- Narendra, V., Rocha, P. P., An, D., Raviram, R., Skok, J. A., Mazzoni, E. O., & Reinberg, D.
- Affiliations
- Howard Hughes Medical Institute (US)
- NYU Langone Health (US)
- New York University (US)
- Corresponding author
- Mazzoni, Esteban O.
- Reinberg, Danny
- ORCID
- Venue
- Science
- Published
- 2015-02-27
- Volume
- 347
- Issue
- 6225
- Pages
- 1017-1021
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4428148
- OpenAlex
- W1975542854
- Cited by
- 535
- References
- 30
- Citations by year
- 2026: 17 · 2025: 20 · 2024: 40 · 2023: 33 · 2022: 44 · 2021: 57 · 2020: 62 · 2019: 54 · 2018: 58 · 2017: 60 · 2016: 56 · 2015: 34
- FWCI
- 29.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R37-37120, GM-64844, T32 GM007238, R01HD079682, GM086852, GM112192)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- CTCF, Hox gene clusters, chromatin insulators, Polycomb group proteins, trithorax group, epigenetic memory, positional identity, embryonic stem cell differentiation, facultative heterochromatin, transcriptional activation
- MeSH terms
- CCCTC-Binding Factor, Animals, Cell Differentiation, Chromatin, Dogs, Gene Expression Regulation, Genes, Homeobox, Multigene Family, Humans, Motor Neurons, Neck, Repressor Proteins, Protein Structure, Tertiary, Mice, Rats, Embryonic Stem Cells
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