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Article

3D Chromatin Organization Involving MEIS1 Factor in the cis-Regulatory Landscape of GJB2

1
University Brest, Inserm, EFS, UMR 1078, GGB, F-29200 Brest, France
2
Laboratoire de Génétique Moléculaire et d’Histocompatibilité, CHRU Brest, UMR 1078, F-29200 Brest, France
*
Authors to whom correspondence should be addressed.
Academic Editors: Cristoforo Comi, Benoit Gauthier, Dimitrios H. Roukos, Alfredo Fusco and Siriluck Ponsuksili
Int. J. Mol. Sci. 2022, 23(13), 6964; https://doi.org/10.3390/ijms23136964
Received: 18 May 2022 / Revised: 17 June 2022 / Accepted: 21 June 2022 / Published: 23 June 2022
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
The human genome is covered by 8% of candidate cis-regulatory elements. The identification of distal acting regulatory elements and an understanding of their action are crucial to determining their key role in gene expression. Disruptions of such regulatory elements and/or chromatin conformation are likely to play a critical role in human genetic diseases. Non-syndromic hearing loss (i.e., DFNB1) is mostly due to GJB2 (Gap Junction Beta 2) variations and DFNB1 large deletions. Although several GJB2 cis-regulatory elements (CREs) have been described, GJB2 gene regulation remains not well understood. We investigated the endogenous effect of these CREs with CRISPR (clustered regularly interspaced short palindromic repeats) disruptions and observed GJB2 expression. To decipher the GJB2 regulatory landscape, we used the 4C-seq technique and defined new chromatin contacts inside the DFNB1 locus, which permit DNA loops and long-range regulation. Moreover, through ChIP-PCR, we determined the involvement of the MEIS1 transcription factor in GJB2 expression. Taken together, the results of our study enable us to describe the 3D DFNB1 regulatory landscape. View Full-Text
Keywords: gene regulation; 3D chromatin organization; enhancer-promoter contacts; CRISPR; 4C; deafness; DFNB1; GJB2; MEIS1 gene regulation; 3D chromatin organization; enhancer-promoter contacts; CRISPR; 4C; deafness; DFNB1; GJB2; MEIS1
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MDPI and ACS Style

Le Nabec, A.; Blotas, C.; Briset, A.; Collobert, M.; Férec, C.; Moisan, S. 3D Chromatin Organization Involving MEIS1 Factor in the cis-Regulatory Landscape of GJB2. Int. J. Mol. Sci. 2022, 23, 6964. https://doi.org/10.3390/ijms23136964

AMA Style

Le Nabec A, Blotas C, Briset A, Collobert M, Férec C, Moisan S. 3D Chromatin Organization Involving MEIS1 Factor in the cis-Regulatory Landscape of GJB2. International Journal of Molecular Sciences. 2022; 23(13):6964. https://doi.org/10.3390/ijms23136964

Chicago/Turabian Style

Le Nabec, Anaïs, Clara Blotas, Alinéor Briset, Mégane Collobert, Claude Férec, and Stéphanie Moisan. 2022. "3D Chromatin Organization Involving MEIS1 Factor in the cis-Regulatory Landscape of GJB2" International Journal of Molecular Sciences 23, no. 13: 6964. https://doi.org/10.3390/ijms23136964

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