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Molecular Biology of AT-Hook Motif Containing Proteins
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Molecular Biology of AT-Hook Motif Containing Proteins

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

Deadline for manuscript submissions: closed (29 June 2024) | Viewed by 3276

Special Issue Editors

Prof. Dr. Manfioletti Guidalberto

E-Mail Website
Guest Editor
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
Interests: high mobility group A (HMGA) proteins; chromatin; regulation of gene expression; protein–protein interactions; post-translational modifications (PTMs); epithelial–mesenchymal transition; proteomics; tumor microenvironment; breast cancer; metastasis
Special Issues, Collections and Topics in MDPI journals
Dr. Riccardo Sgarra

E-Mail Website
Guest Editor
Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
Interests: High Mobility Group A (HMGA) proteins; chromatin; protein-protein interactions; post-translational modifications (PTMs); epigenetic; cancer; mass spectrometry; proteomic
Special Issues, Collections and Topics in MDPI journals
Dr. Monica Fedele

E-Mail Website
Guest Editor
CNR—Institute of Experimental Endocrinology and Oncology, 80131 Naples, Italy
Interests: molecular mechanisms of cancer cell transformation; PATZ1 in development and cancer; animal models; tumor biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The AT-hook is a short DNA-binding protein motif that was first described in the family of High Mobility Group A (HMGA), and is responsible for the name given to this group of proteins. The AT-hook motif consists of a short sequence of 8–9 aminoacids centered around a arginine–glycine–arginine (RGR) peptide and surrounded by positively charged lysine and/or arginine aminoacids that interacts with the minor groove of AT-rich DNA, causing DNA bending involved in chromatin remodeling.

The AT-hook motif has been found in several proteins in a variable number of copies either alone or in combination with other DNA-binding motifs and, in this case, often conferring an auxiliary ability to bind DNA in the minor groove of chromatin factors and DNA-binding proteins, thus contributing to the overall DNA-binding ability of these molecules. Relevant examples of these proteins, besides the members of the HMGA family (HMGA1 and HMGA2), are Brahma related gene 1 (BRG1), POZ/BTB, and AT-hook containing zinc finger 1 (PATZ1), AT-hook transcription factor (AKNA), Snf2 related CREBBP activator protein (SRCAP), methyl-CpG binding protein 2 (MeCP2), AT-hook DNA-binding motif-containing 1 (AHDC1), mixed-lineage-leukemia (MLL), SET binding protein 1 (SETBP1), and INO80 complex subunit B (INO80B), only to mention some. Most of them have been implicated in cancer, possibly suggesting their targeting as anti-cancer strategy.

AT-hook containing proteins have been found in several species ranging from Saccharomyces cerevisiae to Homo sapiens, it is therefore interesting to deepen our knowledge on this large group of proteins at the biochemical and functional level. Papers related to any aspect of AT-hook motifs containing proteins will be considered for this Special Issue.

Prof. Dr. Manfioletti Guidalberto
Dr. Riccardo Sgarra
Dr. Monica Fedele
Guest Editors

Manuscript Submission Information

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Keywords

  • AT-hook
  • Chromatin
  • DNA binding
  • DNA minor groove
  • transcription factors
  • architectural factors
  • chromatin remodeling
  • enhanceosome
  • epigenetic

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Published Papers (2 papers)

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12 pages, 5440 KiB  
Article
Critical Role of the Transcription Factor AKNA in T-Cell Activation: An Integrative Bioinformatics Approach
by Abrahan Ramírez-González, Pedro Ávila-López, Margarita Bahena-Román, Carla O. Contreras-Ochoa, Alfredo Lagunas-Martínez, Elizabeth Langley, Joaquín Manzo-Merino, Vicente Madrid-Marina and Kirvis Torres-Poveda
Int. J. Mol. Sci. 2023, 24(4), 4212; https://doi.org/10.3390/ijms24044212 - 20 Feb 2023
Cited by 1 | Viewed by 1701
Abstract
The human akna gene encodes an AT-hook transcription factor, the expression of which is involved in various cellular processes. The goal of this study was to identify potential AKNA binding sites in genes that participate in T-cell activation and validate selected genes. Here [...] Read more.
The human akna gene encodes an AT-hook transcription factor, the expression of which is involved in various cellular processes. The goal of this study was to identify potential AKNA binding sites in genes that participate in T-cell activation and validate selected genes. Here we analyzed ChIP-seq and microarray assays to determine AKNA-binding motifs and the cellular process altered by AKNA in T-cell lymphocytes. In addition, we performed a validation analysis by RT-qPCR to assess AKNA’s role in promoting IL-2 and CD80 expression. We found five AT-rich motifs that are potential candidates as AKNA response elements. We identified these AT-rich motifs in promoter regions of more than a thousand genes in activated T-cells, and demonstrated that AKNA induces the expression of genes involved in helper T-cell activation, such as IL-2. The genomic enrichment and prediction of AT-rich motif analyses demonstrated that AKNA is a transcription factor that can potentially modulate gene expression by recognizing AT-rich motifs in a plethora of genes that are involved in different molecular pathways and processes. Among the cellular processes activated by AT-rich genes, we found inflammatory pathways potentially regulated by AKNA, suggesting AKNA is acting as a master regulator during T-cell activation. Full article
(This article belongs to the Special Issue Molecular Biology of AT-Hook Motif Containing Proteins)
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Review

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27 pages, 2054 KiB  
Review
Binding to the Other Side: The AT-Hook DNA-Binding Domain Allows Nuclear Factors to Exploit the DNA Minor Groove
by Sabrina Battista, Monica Fedele, Luca Secco, Alberto Maria Davide Ingo, Riccardo Sgarra and Guidalberto Manfioletti
Int. J. Mol. Sci. 2024, 25(16), 8863; https://doi.org/10.3390/ijms25168863 - 14 Aug 2024
Viewed by 754
Abstract
The “AT-hook” is a peculiar DNA-binding domain that interacts with DNA in the minor groove in correspondence to AT-rich sequences. This domain has been first described in the HMGA protein family of architectural factors and later in various transcription factors and chromatin proteins, [...] Read more.
The “AT-hook” is a peculiar DNA-binding domain that interacts with DNA in the minor groove in correspondence to AT-rich sequences. This domain has been first described in the HMGA protein family of architectural factors and later in various transcription factors and chromatin proteins, often in association with major groove DNA-binding domains. In this review, using a literature search, we identified about one hundred AT-hook-containing proteins, mainly chromatin proteins and transcription factors. After considering the prototypes of AT-hook-containing proteins, the HMGA family, we review those that have been studied in more detail and that have been involved in various pathologies with a particular focus on cancer. This review shows that the AT-hook is a domain that gives proteins not only the ability to interact with DNA but also with RNA and proteins. This domain can have enzymatic activity and can influence the activity of the major groove DNA-binding domain and chromatin docking modules when present, and its activity can be modulated by post-translational modifications. Future research on the function of AT-hook-containing proteins will allow us to better decipher their function and contribution to the different pathologies and to eventually uncover their mutual influences. Full article
(This article belongs to the Special Issue Molecular Biology of AT-Hook Motif Containing Proteins)
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