Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping
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Abstract
The Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ , Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Quantitative analysis of chromosome conformation capture assays (3C-qPCR)
Hagège, H., Klous, P., Braem, C., Splinter, E., Dekker, J., Cathala, G., de Laat, W., & Forné, T. (2007) · Nature Protocols · doi:10.1038/nprot.2007.243 · Cited by 720 · cited 1× · see citing works
“3C-PCR was completed as previously described using primers previously designed to study the interaction between the MYC and the NDME locus (Table S1) 8,50–52 , 68 .”
MethodHerranz, D., Ambesi-Impiombato, A., Palomero, T., Schnell, S. A., Belver, L., Wendorff, A. A., Xu, L., Castillo-Martin, M., Llobet-Navás, D., Cordon-Cardo, C., et al. (2014) · Nature Medicine · doi:10.1038/nm.3665 · Cited by 405 · see citing works
Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression
Ghavi-Helm, Y., Jankowski, A., Meiers, S., Viales, R. R., Korbel, J. O., & Furlong, E. E. M. (2019) · Nature Genetics · doi:10.1038/s41588-019-0462-3 · Cited by 354 · see citing works
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- Authors
- Foran, G., Hallam, R. D., Megaly, M., Turgambayeva, A., Antfolk, D., Li, Y., Luca, V. C., & Necakov, A.
- Affiliations
- Brock University (CA)
- Moffitt Cancer Center (US)
- Corresponding author
- Necakov, Aleksandar
- Venue
- Scientific Reports
- Published
- 2024-09-19
- Volume
- 14
- Issue
- 1
- Pages
- 21912-21912
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC11413390
- OpenAlex
- W4402625057
- Cited by
- 11
- References
- 4
- Citations by year
- 2026: 3 · 2025: 8
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada,Canada (PGS-D)
- Natural Sciences and Engineering Research Council of Canada (CGS-D, 2018-06781)
- National Institutes of Health (R35GM133482)
- 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 › RNA Research and Splicing
- Keywords
- Notch1, Notch intracellular domain, phase separation, transcriptional condensates, enhancer looping, super-enhancers, MYC activation, intrinsically disordered regions, transactivation domain, gene expression regulation, nuclear condensates
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