3D Chromatin Organization Involving MEIS1 Factor in the cis-Regulatory Landscape of GJB2.
Int J Mol Sci
; 23(13)2022 Jun 23.
Article
en En
| MEDLINE
| ID: mdl-35805969
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cromatina
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Conexinas
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Sordera
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Conexina 26
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Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2022
Tipo del documento:
Article
País de afiliación:
Francia