Special Issue "Regulating Gene Activity By Sequestering Transcriptional Regulators"

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (1 March 2021).

Special Issue Editors

Dr. Dieter Maier
E-Mail Website
Guest Editor
University Hohenheim, Biology Fg Genetics 190d, 70599 Stuttgart, Germany
Interests: development; evolution; drosophila; notch signaling pathway; cell–cell communication
Dr. Anja Nagel
E-Mail Website
Guest Editor
Department of General Genetics, Institute for Biology 190, University of Hohenheim, 190g, 70593 Stuttgart, Germany
Interests: genetics; gene regulation; Notch signaling; Drosophila; transcriptional super complexes

Special Issue Information

In eukaryotes, gene transcription occurs within the nucleus. Accordingly, transcriptional regulators must enter the nuclear compartment. Numerous regulatory mechanisms guard the nuclear import or export of transcriptional regulators or their co-factors. Sequestering transcriptional regulators in a specific subcellular compartment is one mechanism to control their availability. Prime examples are the regulation of NF-κB nuclear entry by IκB, the cytoplasmic anchoring of cleaved Ci/Gli during Hedgehog signalling or of ß-Cat during Wnt signaling, as well as the co-import of RBPJ (or CBF1) by co-repressors and co-activators during Notch signaling. These examples represent a small sample of transcription factors, where nuclear entry is tightly controlled. Not surprisingly, the factors guarding nuclear import or export are themselves subjected to a dose-sensitive regulation.

This Special Issue will focus on the sequestering of transcriptional regulators for experimental or therapeutic intervention, including specific techniques to abrogate the function of nuclear proteins in a reversible manner. We invite submissions of reviews, research articles, and short communications on related topics by 1 March 2021. 

Dr. Dieter Maier
Dr. Anja Nagel
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Gene regulation
  • Genetics
  • Transcriptional regulation
  • Transcription complexes
  • Sequestering
  • Overexpression
  • Pathways

Published Papers (2 papers)

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Research

Article
Membrane-Anchored Hairless Protein Restrains Notch Signaling Activity
Genes 2020, 11(11), 1315; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11111315 - 06 Nov 2020
Viewed by 747
Abstract
The Notch signaling pathway governs cell-to-cell communication in higher eukaryotes. In Drosophila, after cleavage of the transmembrane receptor Notch, the intracellular domain of Notch (ICN) binds to the transducer Suppressor of Hairless (Su(H)) and shuttles into the nucleus to activate Notch target [...] Read more.
The Notch signaling pathway governs cell-to-cell communication in higher eukaryotes. In Drosophila, after cleavage of the transmembrane receptor Notch, the intracellular domain of Notch (ICN) binds to the transducer Suppressor of Hairless (Su(H)) and shuttles into the nucleus to activate Notch target genes. Similarly, the Notch antagonist Hairless transfers Su(H) into the nucleus to repress Notch target genes. With the aim to prevent Su(H) nuclear translocation, Hairless was fused to a transmembrane domain to anchor the protein at membranes. Indeed, endogenous Su(H) co-localized with membrane-anchored Hairless, demonstrating their binding in the cytoplasm. Moreover, adult phenotypes uncovered a loss of Notch activity, in support of membrane-anchored Hairless sequestering Su(H) in the cytosol. A combined overexpression of membrane-anchored Hairless with Su(H) lead to tissue proliferation, which is in contrast to the observed apoptosis after ectopic co-overexpression of the wild-type genes, indicating a shift to a gain of Notch activity. A mixed response, general de-repression of Notch signaling output, plus inhibition at places of highest Notch activity, perhaps reflects Su(H)’s role as activator and repressor, supported by results obtained with the Hairless-binding deficient Su(H)LLL mutant, inducing activation only. Overall, the results strengthen the idea of Su(H) and Hairless complex formation within the cytosolic compartment. Full article
(This article belongs to the Special Issue Regulating Gene Activity By Sequestering Transcriptional Regulators)
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Article
Limited Availability of General Co-Repressors Uncovered in an Overexpression Context during Wing Venation in Drosophila melanogaster
Genes 2020, 11(10), 1141; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11101141 - 28 Sep 2020
Cited by 1 | Viewed by 1007
Abstract
Cell fate is determined by the coordinated activity of different pathways, including the conserved Notch pathway. Activation of Notch results in the transcription of Notch targets that are otherwise silenced by repressor complexes. In Drosophila, the repressor complex comprises the transcription factor [...] Read more.
Cell fate is determined by the coordinated activity of different pathways, including the conserved Notch pathway. Activation of Notch results in the transcription of Notch targets that are otherwise silenced by repressor complexes. In Drosophila, the repressor complex comprises the transcription factor Suppressor of Hairless (Su(H)) bound to the Notch antagonist Hairless (H) and the general co-repressors Groucho (Gro) and C-terminal binding protein (CtBP). The latter two are shared by different repressors from numerous pathways, raising the possibility that they are rate-limiting. We noted that the overexpression during wing development of H mutants HdNT and HLD compromised in Su(H)-binding induced ectopic veins. On the basis of the role of H as Notch antagonist, overexpression of Su(H)-binding defective H isoforms should be without consequence, implying different mechanisms but repression of Notch signaling activity. Perhaps excess H protein curbs general co-repressor availability. Supporting this model, nearly normal wings developed upon overexpression of H mutant isoforms that bound neither Su(H) nor co-repressor Gro and CtBP. Excessive H protein appeared to sequester general co-repressors, resulting in specific vein defects, indicating their limited availability during wing vein development. In conclusion, interpretation of overexpression phenotypes requires careful consideration of possible dominant negative effects from interception of limiting factors. Full article
(This article belongs to the Special Issue Regulating Gene Activity By Sequestering Transcriptional Regulators)
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