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Cited by 10Genomics and Chromatin DynamicsGenomic variations and chromosomal abnormalitiesNuclear Structure and Function

From FISH to Hi-C: The Chromatin Architecture of the Chromosomal Region 7q36.3, Frequently Rearranged in Leukemic Cells, Is Evolutionary Conserved

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Gulino, Gesualda M., Bruno, Francesca, Sturiale, Valentina, Brancato, Desiree, Ragusa, Denise, Tosi, Sabrina, Saccone, Salvatore, Federico, Concetta·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms22052338PMC PMC7956786
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Abstract

Fluorescence in situ hybridization (FISH) and Hi-C methods are largely used to investigate the three-dimensional organization of the genome in the cell nucleus and are applied here to study the organization of genes (LMBR1, NOM1, MNX1, UBE3C, PTPRN2) localized in the human 7q36.3 band. This region contains the MNX1 gene, which is normally not expressed in human lymphocytes beyond embryonic development. However, this homeobox gene is frequently activated in leukemic cells and its expression is associated with an altered gene positioning in the leukemia cell nuclei. In this study, we used FISH on 3D-preserved nuclei to investigate the nuclear positioning of MNX1 in the leukemia-derived cell line K562. Of the five copies of the MNX1 gene present in K562, four alleles were positioned in the nuclear periphery and only one in the nuclear interior. Using the Juicebox’s Hi-C dataset, we identified five chromatin loops in the 7q36.3 band, with different extensions related to the size and orientation of the genes located here, and independent from their expression levels. We identified similar loops in 11 human and three mouse cell lines, showing that these loops are highly conserved in different human cell lines and during evolution. Moreover, the chromatin loop organization is well conserved also during neuronal cell differentiation, showing consistency in genomic organization of this region in development. In this report, we show that FISH and Hi-C are two different approaches that complement one another and together give complete information on the nuclear organization of specific chromosomal regions in different conditions, including cellular differentiation and genetic diseases.

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  • Genes arising in AT-rich, heterochromatic regions often remain silenced or are eventually lost.

    “Genes arising in GC-rich, euchromatic regions are more likely to become functional and fixed, whereas those in AT-rich, heterochromatic regions often remain silenced or are eventually lost [71,72,73].”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [71]

    The Introduction (page unavailable) describes closed-chromatin compartment B as gene-poor and having properties opposite to the highly expressed genes in open-chromatin compartment A. That supports an association with lower expression, but the paper does not establish that genes arising in AT-rich regions often remain silenced or are eventually lost. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • The chromatin and nuclear context in which a new gene emerges can strongly influence its evolutionary trajectory.

    “Recent research suggests that the chromatin and nuclear context in which a new gene emerges can strongly influence its evolutionary trajectory.”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [71]

    The Conclusions (page unavailable) link chromatin organization and nuclear position to gene expression, and the Discussion reports conserved chromatin-loop organization in the human and mouse regions studied. The paper does not address where new genes emerge or show that their chromatin or nuclear context influences their evolutionary trajectory. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Genes arising in GC-rich, euchromatic regions are more likely to become functional and fixed.

    “Genes arising in GC-rich, euchromatic regions are more likely to become functional and fixed, whereas those in AT-rich, heterochromatic regions often remain silenced or are eventually lost [71,72,73].”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [71]

    The Introduction (page not available in our copy) describes open-chromatin compartments as gene-dense and containing highly expressed genes. It does not say that genes arising in GC-rich regions are more likely to become functional or fixed; it addresses gene expression, not the evolutionary fate of newly arising genes. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 26

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Authors
Gulino, G. M., Bruno, F., Sturiale, V., Brancato, D., Ragusa, D., Tosi, S., Saccone, S., & Federico, C.
Affiliations
  • University of Catania (IT)
  • Brunel University of London (GB)
Corresponding author
  • Saccone, Salvatore
  • Federico, Concetta
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-02-26
Volume
22
Issue
5
Pages
2338
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms22052338
PMC
PMC7956786
OpenAlex
W3134368273
Cited by
10
References
31
Citations by year
2025: 4 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 1
FWCI
0.47
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Brunel University Research Archive (BURA) (Brunel University London) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Department of Biological, Geological and Environmental Sciences, University of Catania (Research Plan PIACERI L.3 Starting Grant to C.F.)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
chromatin structure, 3D genome organization, MNX1, chromatin looping, leukemia, K562 cells, evolutionary conservation, neuronal differentiation, LMBR1, UBE3C, PTPRN2, nuclear positioning
MeSH terms
Animals, Cell Nucleus, Chromatin, Chromosomes, Human, Multigene Family, Humans, Leukemia, Transcription Factors, In Situ Hybridization, Fluorescence, Homeodomain Proteins, Cell Line, Tumor, Mice

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