The DOI matches its Crossref record; 33 of the 35 references it cites were found in a registry or an index.
CTCF/cohesin-mediated DNA looping is required for protocadherin α promoter choice
Open accessAbstract
The closely linked human protocadherin ( Pcdh ) α, β, and γ gene clusters encode 53 distinct protein isoforms, which are expressed in a combinatorial manner to generate enormous diversity on the surface of individual neurons. This diversity is a consequence of stochastic promoter choice and alternative pre-mRNA processing. Here, we show that Pcdhα promoter choice is achieved by DNA looping between two downstream transcriptional enhancers and individual promoters driving the expression of alternate Pcdhα isoforms. In addition, we show that this DNA looping requires specific binding of the CTCF/cohesin complex to two symmetrically aligned binding sites in both the transcriptionally active promoters and in one of the enhancers. These findings have important implications regarding enhancer/promoter interactions in the generation of complex Pcdh cell surface codes for the establishment of neuronal identity and self-avoidance in individual neurons.
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In the citing paper
“In the classic scenario, this boundary is presented by CTCF binding to its sequence motifs located in a divergent orientation at either end of the loop [277, 438–440]”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [438]
In the citing paper
“In the mammalian protocadherin α (Pcdhα) gene cluster, each promoter contains a CTCF binding site capable of looping with a convergent CTCF binding site on the enhancer.”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [140]
In the citing paper
“Selective demethylation of the CTCF binding site on a particular promoter allows that promoter to establish contact with the enhancer, resulting in activation of the expression of that particular Pcdhα gene [140,141].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [140]
In the citing paper
“However, the CTCF sites on the promoters are methylated, preventing CTCF binding and looping.”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [140]
Citations
Cites
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450
Mediator and cohesin connect gene expression and chromatin architecture
Kagey, M. H., Newman, J. J., Bilodeau, S., Zhan, Y., Orlando, D. A., van Berkum, N. L., Ebmeier, C. C., Goossens, J., Rahl, P. B., Levine, S. S., et al. (2010) · Nature · doi:10.1038/nature09380 · Cited by 1,939
Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene
Bell, A. C., & Felsenfeld, G. (2000) · Nature · doi:10.1038/35013100 · Cited by 1,746
CTCF: Master Weaver of the Genome
Phillips‐Cremins, J. E., & Corces, V. G. (2009) · Cell · doi:10.1016/j.cell.2009.06.001 · Cited by 1,585
CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus
Hark, A. T., Schoenherr, C. J., Katz, D. J., Ingram, R. S., Levorse, J. M., & Tilghman, S. M. (2000) · Nature · doi:10.1038/35013106 · Cited by 1,547
Cohesin mediates transcriptional insulation by CCCTC-binding factor
Wendt, K. S., Yoshida, K., Itoh, T., Bando, M., Koch, B., Schirghuber, E., Tsutsumi, S., Nagae, G., Ishihara, K., Mishiro, T., et al. (2008) · Nature · doi:10.1038/nature06634 · Cited by 1,193
Cohesin: Its Roles and Mechanisms
Nasmyth, K., & Haering, C. H. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102108-134233 · Cited by 1,015
Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones.
Biedler, J. L., Roffler-Tarlov, S. K., Schachner, M., & Freedman, L. S. (1978) · PubMed · Cited by 759
A Striking Organization of a Large Family of Human Neural Cadherin-like Cell Adhesion Genes
Wu, Q., & Maniatis, T. (1999) · Cell · doi:10.1016/s0092-8674(00)80789-8 · Cited by 722
Self-citation
Cited by
Sorted by citations
CTCF: an architectural protein bridging genome topology and function
Ong, C., & Corces, V. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3663 · Cited by 1,094
CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function
Guo, Y., Xu, Q., Canzio, D., Shou, J., Li, J., Gorkin, D. U., Jung, I., Wu, H., Zhai, Y., Tang, Y., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.038 · Cited by 958
Self-citationThree-dimensional genome architecture: players and mechanisms
Pombo, A., & Dillon, N. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3965 · Cited by 603
Genome folding through loop extrusion by SMC complexes
Davidson, I. F., & Peters, J. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00349-7 · Cited by 531
Looping Back to Leap Forward: Transcription Enters a New Era
Levine, M., Cattoglio, C., & Tjian, R. (2014) · Cell · doi:10.1016/j.cell.2014.02.009 · Cited by 497
Metadata
- Authors
- Guo, Y., Monahan, K., Wu, H., Gertz, J., Varley, K. E., Li, W., Myers, R. M., Maniatis, T., & Wu, Q.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Columbia University (US)
- HudsonAlpha Institute for Biotechnology (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-11-30
- Volume
- 109
- Issue
- 51
- Pages
- 21081-21086
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3529044
- OpenAlex
- W2013934108
- Cited by
- 258
- References
- 35
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 24 · 2023: 16 · 2022: 11 · 2021: 21 · 2020: 17 · 2019: 21 · 2018: 21 · 2017: 23 · 2016: 19 · 2015: 20 · 2014: 16 · 2013: 23
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS043915)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- DNA looping, CTCF, cohesin, enhancer-promoter interactions, alternative splicing, isoform diversity, neuronal identity, self-avoidance, enhancers
- MeSH terms
- CCCTC-Binding Factor, Cohesins, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Models, Biological, Models, Genetic, Neurons, Nuclear Proteins, Phosphoproteins, Promoter Regions, Genetic, Repressor Proteins, Stochastic Processes, Transcription, Genetic, Cadherins, Cell Cycle Proteins, CpG Islands, Protein Isoforms, Epigenesis, Genetic
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