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. 2023 Jan 25:14:1129207.
doi: 10.3389/fgene.2023.1129207. eCollection 2023.

Chromosome conformation capture approaches to investigate 3D genome architecture in Ankylosing Spondylitis

Connor Davidson  1   2 , B Paul Wordsworth  2 , Carla J Cohen  2   3 , Julian C Knight  1 , Matteo Vecellio  2   4
Affiliations

Chromosome conformation capture approaches to investigate 3D genome architecture in Ankylosing Spondylitis

Connor Davidson et al. Front Genet. .

Abstract

Ankylosing Spondylitis (AS) is a chronic inflammatory arthritis of the spine exhibiting a strong genetic background. The mechanistic and functional understanding of the AS-associated genomic loci, identified with Genome Wide Association Studies (GWAS), remains challenging. Chromosome conformation capture (3C) and derivatives are recent techniques which are of great help in elucidating the spatial genome organization and of enormous support in uncover a mechanistic explanation for disease-associated genetic variants. The perturbation of three-dimensional (3D) genome hierarchy may lead to a plethora of human diseases, including rheumatological disorders. Here we illustrate the latest approaches and related findings on the field of genome organization, highlighting how the instability of 3D genome conformation may be among the causes of rheumatological disease phenotypes. We suggest a new perspective on the inclusive potential of a 3C approach to inform GWAS results in rheumatic diseases. 3D genome organization may ultimately lead to a more precise and comprehensive functional interpretation of AS association, which is the starting point for emerging and more specific therapies.

Keywords: ankylosing spondylitis; chromosome conformation capture (3C); genomics; rheumatic and musculoskeletal disease; three dimensional genome; topologically associated domain (TAD).

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Conflict of interest statement

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

Figures

FIGURE 1
FIGURE 1
TADs insulation. Simplified model showing how topologically associated domains (TADs) are insulated by borders which are leaky enough to influence and regulate nearby genes expression (Luppino et al., 2020).
FIGURE 2
FIGURE 2
The loop-extrusion model. The model shows the generation of long-range cis-interactions, following extrusion by cohesin, CTCF cognate sites binding and involvement of other accessory proteins including YY1, RAD21 and ZNF143 (Hansen et al., 2018).
See this image and copyright information in PMC

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References

    1. Al-Husini N., Medler S., Ansari A. (2020). Crosstalk of promoter and terminator during RNA polymerase II transcription cycle. Biochim. Biophys. Acta Gene Regul. Mech. 1863 (12), 194657. 10.1016/j.bbagrm.2020.194657 - DOI - PubMed
    1. Al-Mossawi H., Coates L. C. (2018). Personalized medicine - a new reality in psoriatic arthritis? Nat. Rev. Rheumatol. 14 (8), 449–451. 10.1038/s41584-018-0043-3 - DOI - PubMed
    1. Aljahani A., Hua P., Karpinska M. A., Quililan K., Davies J. O. J., Oudelaar A. M. (2022). Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF. Nat. Commun. 13 (1), 2139. 10.1038/s41467-022-29696-5 - DOI - PMC - PubMed
    1. Anania C., Lupianez D. G. (2020). Order and disorder: Abnormal 3D chromatin organization in human disease. Brief. Funct. Genomics 19 (2), 128–138. 10.1093/bfgp/elz028 - DOI - PMC - PubMed
    1. Baeten D., Baraliakos X., Braun J., Sieper J., Emery P., van der Heijde D., et al. (2013). Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: A randomised, double-blind, placebo-controlled trial. Lancet 382 (9906), 1705–1713. 10.1016/S0140-6736(13)61134-4 - DOI - PubMed