Skip to main content

EDITORIAL article

Front. Cell Dev. Biol., 06 December 2023
Sec. Nuclear Organization and Dynamics
This article is part of the Research Topic Editors' Showcase 2022-2023: Insights in Nuclear Organization and Dynamics View all 5 articles

Editorial: Editors’ showcase 2022-2023: insights in nuclear organization and dynamics

  • Institute of Cell Biology, University of Edinburgh, Edinburgh, United Kingdom

The Section on Nuclear Organization and Dynamics has a wide range of expertise on its Editorial and Reviewer Boards and we have captured a snapshot of this in the set of papers highlighted in this Editor’s Showcase.

Zelenka et al. in previous studies of the T-cell CD4+/CD8+ stage of development had noted that the transcription factor SATB1 had additional functional roles (Cai et al., 2003; Feng et al., 2022; Zelenka et al., 2022). They postulated that these roles might be supported by another splice variant of SATB1 and in “A novel SATB1 protein isoform with different biophysical properties” they identified this novel variant. Apart from a beautiful characterization of this novel splice variant that included super-resolution microscopy imaging and identification of many interacting proteins, they found that it phase separates and does so in a manner regulated by phosphorylation. Notably, they also found it binds to non-coding RNAs and it has recently been demonstrated by Nobel Laureate Phil Sharp and others (Zhang et al., 2015; Sharp et al., 2022) that RNA binding can also drive phase separation. They demonstrated a propensity to phase separate for both the previous and novel isoforms, but further showed that an additional exon in the novel isoform also contained a prion-like domain that further enhances its phase-separation capabilities. In comparing ATAC-Seq cancer data, they found that the accessibility of the extra exon in the novel isoform (implying its expression) correlates with better outcomes in several cancers. Finally, consistent with splicing proteins being amongst its identified interacting proteins, the new SATB1 isoform seems to regulate its own splicing. These findings are important not just in their own right, but because after over a quarter century studying this transcription factor and massive amounts of high-throughput sequencing studies, a new splice variant can still be found. Editors at the Section on Nuclear Organization and Dynamics anticipate that there are thousands of as yet unidentified tissue- and developmental stage-specific splice variants and encourage papers identifying them as well as papers identifying new drivers of phase separation.

Stephenson-Gussinye and Furlan-Magaril presented an insightful overview of the evolving field using “Chromosome conformation capture technologies as tools to detect structural variations and their repercussion in chromatin 3D configuration.” Historically translocations were identified by chromosome spreads and subsequently through fusion points identified by genome sequencing; however, since 4C was first used on primary cancers in 2009 (Simonis et al., 2009), it has revolutionized the identification of these and other structural variations (SVs) by also revealing data about how the change affects regulation in adjacent regions, e.g., altering super-enhancer interactions that regulate expression of multiple genes that can contribute to the original cancer—for example, a gene hub supporting cell migration to drive metastasis. However, even less expensive techniques such as 3C can give much information about SVs in cancers that can inform on patient treatments and expected progression.

The labs of Hoboth et al. developed a way that the many millions of formalin fixed and paraffin embedded (FFPE) tissue sections can be used for quantitative multi-parameter investigations. In “Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts,” they developed protocols for using such samples to quantify nuclear phosphatidylinositol 4,5-bisphosphate (nPI(4,5)P2) levels within the nuclear speckle compartment. The authors had previously shown by that nPI(4,5)P2 levels are elevated in human papillomavirus (HPV)-associated cancer (Marx et al., 2018) and wondered if a staining protocol could be developed for use diagnostically as well as if it is similarly upregulated in HPV-induced warts that sometimes become malignant (Howley and Pfister, 2015). Stimulated emission depletion (STED) microscopy (Hell and Wichmann, 1994; Klar et al., 2000) is amongst the highest resolution super resolution microscopy approaches, while still being comparatively easy to use. They adapted a staining protocol for use with FFPE tissue sections to mark both nPI(4,5)P2 and nuclear speckles using STED. The paper is worth reading for the shear beauty of the staining alone, but they moreover demonstrated the increase in co-localization of the nPI(4,5)P2 and a nuclear speckle marker in HPV-induced warts compared to healthy skin. This suggests that similar markers could be used to distinguish disease samples and potentially even prognostically grade tumors.

Rush et al. presented a beautifully balanced overview of different models for nucleo-cytoplasmic transport in “Unveiling the complexity: assessing models describing the structure and function of the nuclear pore complex.” Notably, the beautiful historical overview highlights a number of misconceptions from oversimplification such as the typical textbook descriptions implying a rigid diffusion barrier when its nature is quite dynamic. This review is also very valuable in its accuracy and clear descriptions of the limitations of some of the techniques used to generate the data on which transport models are derived. This review is the most comprehensive I have encountered covering the Plug (Talcott and Moore, 1999), Polymer Brush (Rout et al., 2003), Oily Spaghetti (Macara, 2001), Hydrogel (Ribbeck and Gorlich, 2001), Reduction of Dimensionality (Peters, 2005), Forest (Yamada et al., 2010), Gradient (Ben-Efraim and Gerace, 2001), Dilation (Oberleithner et al., 2000), and Transport Receptor (Lim et al., 2006) models for central channel transport. In addition, mechanisms of transmembrane transport through the peripheral NPC channels are also described.

These papers highlight both the excellence and wide range of expertise among our editors at Frontiers. It should be noted that in addition to these great studies and reviews, Frontiers Nuclear Organization and Dynamics editors have contributed many excellent studies to many other Research Topics over the past year.

Author contributions

ES: Conceptualization, Writing–original draft, Writing–review and editing.

Conflict of interest

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Ben-Efraim, I., and Gerace, L. (2001). Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import. J. Cell Biol. 152, 411–417. doi:10.1083/jcb.152.2.411

PubMed Abstract | CrossRef Full Text | Google Scholar

Cai, S., Han, H.-J., and Kohwi-Shigematsu, T. (2003). Tissue-specific nuclear architecture and gene expression regulated by SATB1. Nat. Genet. 34, 42–51. doi:10.1038/ng1146

PubMed Abstract | CrossRef Full Text | Google Scholar

Feng, D., Chen, Y., Dai, R., Bian, S., Xue, W., Zhu, Y., et al. (2022). Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by regulating the activity of super-enhancers. Nat. Commun. 13, 5554. doi:10.1038/s41467-022-33333-6

PubMed Abstract | CrossRef Full Text | Google Scholar

Hell, S. W., and Wichmann, J. (1994). Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. Opt. Lett. 19, 780–782. doi:10.1364/ol.19.000780

PubMed Abstract | CrossRef Full Text | Google Scholar

Howley, P. M., and Pfister, H. J. (2015). Beta genus papillomaviruses and skin cancer. Virology 479-480, 290–296. doi:10.1016/j.virol.2015.02.004

PubMed Abstract | CrossRef Full Text | Google Scholar

Klar, T. A., Jakobs, S., Dyba, M., Egner, A., and Hell, S. W. (2000). Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. Proc. Natl. Acad. Sci. U. S. A. 97, 8206–8210. doi:10.1073/pnas.97.15.8206

PubMed Abstract | CrossRef Full Text | Google Scholar

Lim, R. Y., Huang, N. P., Koser, J., Deng, J., Lau, K. H., Schwarz-Herion, K., et al. (2006). Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport. Proc. Natl. Acad. Sci. U. S. A. 103, 9512–9517. doi:10.1073/pnas.0603521103

PubMed Abstract | CrossRef Full Text | Google Scholar

Macara, I. G. (2001). Transport into and out of the nucleus. Microbiol. Mol. Biol. Rev. 65, 570–594. doi:10.1128/MMBR.65.4.570-594.2001

PubMed Abstract | CrossRef Full Text | Google Scholar

Marx, B., Hufbauer, M., Zigrino, P., Majewski, S., Markiefka, B., Sachsenheimer, T., et al. (2018). Phospholipidation of nuclear proteins by the human papillomavirus E6 oncoprotein: implication in carcinogenesis. Oncotarget 9, 34142–34158. doi:10.18632/oncotarget.26140

PubMed Abstract | CrossRef Full Text | Google Scholar

Oberleithner, H., Schillers, H., Wilhelmi, M., Butzke, D., and Danker, T. (2000). Nuclear pores collapse in response to CO2 imaged with atomic force microscopy. Pflugers Archiv Eur. J. physiology 439, 251–255. doi:10.1007/s004249900183

PubMed Abstract | CrossRef Full Text | Google Scholar

Peters, R. (2005). Translocation through the nuclear pore complex: selectivity and speed by reduction-of-dimensionality. Traffic 6, 421–427. doi:10.1111/j.1600-0854.2005.00287.x

PubMed Abstract | CrossRef Full Text | Google Scholar

Ribbeck, K., and Gorlich, D. (2001). Kinetic analysis of translocation through nuclear pore complexes. EMBO J. 20, 1320–1330. doi:10.1093/emboj/20.6.1320

PubMed Abstract | CrossRef Full Text | Google Scholar

Rout, M. P., Aitchison, J. D., Magnasco, M. O., and Chait, B. T. (2003). Virtual gating and nuclear transport: the hole picture. Trends Cell Biol. 13, 622–628. doi:10.1016/j.tcb.2003.10.007

PubMed Abstract | CrossRef Full Text | Google Scholar

Sharp, P. A., Chakraborty, A. K., Henninger, J. E., and Young, R. A. (2022). RNA in formation and regulation of transcriptional condensates. RNA 28, 52–57. doi:10.1261/rna.078997.121

PubMed Abstract | CrossRef Full Text | Google Scholar

Simonis, M., Klous, P., Homminga, I., Galjaard, R.-J., Rijkers, E.-J., Grosveld, F., et al. (2009). High-resolution identification of balanced and complex chromosomal rearrangements by 4C technology. Nat. methods 6, 837–842. doi:10.1038/nmeth.1391

PubMed Abstract | CrossRef Full Text | Google Scholar

Talcott, B., and Moore, M. S. (1999). Getting across the nuclear pore complex. Trends Cell Biol. 9, 312–318. doi:10.1016/s0962-8924(99)01608-6

PubMed Abstract | CrossRef Full Text | Google Scholar

Yamada, J., Phillips, J. L., Patel, S., Goldfien, G., Calestagne-Morelli, A., Huang, H., et al. (2010). A bimodal distribution of two distinct categories of intrinsically disordered structures with separate functions in FG nucleoporins. Mol. Cell. proteomics MCP 9, 2205–2224. doi:10.1074/mcp.M000035-MCP201

PubMed Abstract | CrossRef Full Text | Google Scholar

Zelenka, T., Klonizakis, A., Tsoukatou, D., Papamatheakis, D.-A., Franzenburg, S., Tzerpos, P., et al. (2022). The 3D enhancer network of the developing T cell genome is shaped by SATB1. Nat. Commun. 13, 6954. doi:10.1038/s41467-022-34345-y

PubMed Abstract | CrossRef Full Text | Google Scholar

Zhang, H., Elbaum-Garfinkle, S., Langdon, E. M., Taylor, N., Occhipinti, P., Bridges, A. A., et al. (2015). RNA controls polyQ protein phase transitions. Mol. Cell 60, 220–230. doi:10.1016/j.molcel.2015.09.017

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: Satb1, condensates, strutural variations, cancer, super resolution microscopy, nuclear pore complex (NPC), nucleo-cytoplasmic transport

Citation: Schirmer EC (2023) Editorial: Editors’ showcase 2022-2023: insights in nuclear organization and dynamics. Front. Cell Dev. Biol. 11:1340745. doi: 10.3389/fcell.2023.1340745

Received: 18 November 2023; Accepted: 29 November 2023;
Published: 06 December 2023.

Edited and reviewed by:

Amanda Gay Fisher, University of Oxford, United Kingdom

Copyright © 2023 Schirmer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Eric C. Schirmer, e.schirmer@ed.ac.uk

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.