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Special Issue "Zinc-Finger Proteins in Health and Disease"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Prof. Dr. Ciro Abbondanza
E-Mail Website
Co-Guest Editor
Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio, 80138 Naples, Italy
Interests: cancers; PRDM genes; steroid receptors
Special Issues and Collections in MDPI journals
Dr. Erika Di Zazzo
E-Mail Website1 Website2
Co-Guest Editor
Department of Medicine and Health Science, University of Molise, 86100 Campobasso, Italy
Interests: cancers; PRDM genes; steroid receptors; signal transduction
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Proteins containing Zinc-finger domain(s) (ZFP) are able to mediate the interaction with DNA, RNA, and other proteins. They are implicated in transcriptional regulation, ubiquitin-mediated protein degradation, signal transduction, DNA repair, cell migration, and numerous other processes. Besides, many of these proteins function through epigenetic modifications such as DNA methylation and histone modifications, which regulate transcription in physiological and pathological conditions.

The number and the type of zinc fingers in a single protein can be highly variable, thus allowing also a great variability of targets. The Cys2His2 type represents the classical and most abundant zinc finger motif, and it is present in over 700 proteins in humans, with many of them functioning as transcription factors. Among them, the well-known CTCF protein, an important regulator of chromatin organization, contains 11 highly conserved zinc-finger motifs and it plays a central role in the control of gene expression by stabilizing the enhancer-promoter interaction.

Of note, these proteins often contain multiple additional domains other than zinc-fingers. Indeed, in metazoan zinc-finger domains are rarely found alone and usually form tandem arrays combined with different domains thus further increasing their complexity and potential functions. These domains include Krüppel-associated box (KRAB), SCAN, the zinc finger-associated domain (ZAD) among the others. Likewise, members of the positive regulatory domain (PRDM) family gene are characterized by a PR domain, related to the SET methyltransferase domain, and multiple zinc fingers motifs. PRDM proteins are able to modulate the expression of target genes by modifying the chromatin structure either directly, through their intrinsic methyltransferase activity, or indirectly, through the recruitment of specific chromatin remodeling complexes. The PRDM gene family is involved in a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, stemness and maintenance of immune cell homeostasis, being implicated in the transduction of several signals. Remarkably, given this wide range of functions, their disruption may contribute to the onset and progression of several human diseases. Similarly, other ZFPs, such as GATA family proteins and Nuclear Receptors among the others, have been established to play a pathophysiological role in humans.

We invite authors to submit both original research articles and review articles that cover recent research advances in the understanding of the molecular mechanisms of transcriptional regulation and main processes controlled by ZFPs during the development, cell homeostasis maintenance, as well as in the onset and progression of human disease.

Dr. Amelia Casamassimi
Guest Editor
Dr. Monica Rienzo
Prof. Dr. Ciro Abbondanza
Dr. Erika Di Zazzo
Co-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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Zinc-finger domain
  • CTCF
  • PRDM family
  • GATA family
  • Nuclear receptors
  • Human diseases
  • Gene expression regulation
  • Epigenetic modifications

Published Papers (1 paper)

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Research

Article
ZNF521 Enhances MLL-AF9-Dependent Hematopoietic Stem Cell Transformation in Acute Myeloid Leukemias by Altering the Gene Expression Landscape
Int. J. Mol. Sci. 2021, 22(19), 10814; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910814 - 06 Oct 2021
Viewed by 321
Abstract
Leukemias derived from the MLL-AF9 rearrangement rely on dysfunctional transcriptional networks. ZNF521, a transcription co-factor implicated in the control of hematopoiesis, has been proposed to sustain leukemic transformation in collaboration with other oncogenes. Here, we demonstrate that ZNF521 mRNA levels correlate with specific [...] Read more.
Leukemias derived from the MLL-AF9 rearrangement rely on dysfunctional transcriptional networks. ZNF521, a transcription co-factor implicated in the control of hematopoiesis, has been proposed to sustain leukemic transformation in collaboration with other oncogenes. Here, we demonstrate that ZNF521 mRNA levels correlate with specific genetic aberrations: in particular, the highest expression is observed in AMLs bearing MLL rearrangements, while the lowest is detected in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. In cord blood-derived CD34+ cells, enforced expression of ZNF521 provides a significant proliferative advantage and enhances MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome analysis of primary CD34+ cultures displayed subsets of genes up-regulated by MLL-AF9 or ZNF521 single transgene overexpression as well as in MLL-AF9/ZNF521 combinations, at either the early or late time points of an in vitro leukemogenesis model. The silencing of ZNF521 in the MLL-AF9 + THP-1 cell line coherently results in an impairment of growth and clonogenicity, recapitulating the effects observed in primary cells. Taken together, these results underscore a role for ZNF521 in sustaining the self-renewal of the immature AML compartment, most likely through the perturbation of the gene expression landscape, which ultimately favors the expansion of MLL-AF9-transformed leukemic clones. Full article
(This article belongs to the Special Issue Zinc-Finger Proteins in Health and Disease)
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