Integration of high-throughput reporter assays identify a critical enhancer of the Ikzf1 gene.
Fiche publication
Date publication
janvier 2020
Journal
PloS one
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SEXTON Thomas
Tous les auteurs :
Alomairi J, Molitor AM, Sadouni N, Hussain S, Torres M, Saadi W, Dao LTM, Charbonnier G, Santiago-Algarra D, Andrau JC, Puthier D, Sexton T, Spicuglia S
Lien Pubmed
Résumé
The Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/Ikzf1 is involved in leukemia. Tissue-specific and cell identity genes are usually associated with clusters of enhancers, also called super-enhancers, which are believed to ensure proper regulation of gene expression throughout cell development and differentiation. Several potential regulatory regions have been identified in close proximity of Ikzf1, however, the full extent of the regulatory landscape of the Ikzf1 locus is not yet established. In this study, we combined epigenomics and transcription factor binding along with high-throughput enhancer assay and 4C-seq to prioritize an enhancer element located 120 kb upstream of the Ikzf1 gene. We found that deletion of the E120 enhancer resulted in a significant reduction of Ikzf1 mRNA. However, the epigenetic landscape and 3D topology of the locus were only slightly affected, highlighting the complexity of the regulatory landscape regulating the Ikzf1 locus.
Référence
PLoS ONE. 2020 ;15(5):e0233191