Integration of high-throughput reporter assays identify a critical enhancer of the Ikzf1 gene

Jaafar Alomairi (1) , Anne Molitor (2) , Nori Sadouni (1) , Saadat Hussain (1) , Magali Torres (1) , Wiam Saadi (1) , Lan Dao (1) , Guillaume Charbonnier (1) , David Santiago-Algarra (1) , Jean Christophe Andrau (3) , Denis Puthier (1) , Tom Sexton (4) , Salvatore Spicuglia (1)

1 TAGC - Theories and Approaches of Genomic Complexity
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
3 IGMM - Institut de Génétique Moléculaire de Montpellier
4 IGH - Institut de génétique humaine

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-through-put 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.

Mots clés: Polymerase chain reaction; Transcription factors; Genomic signal processing; Chromatin; Gene regulation; Enhancer elements; Thymocytes; Genetic loci

Domaines: Sciences du Vivant [q-bio]; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Bio-Informatique, Biologie Systémique [q-bio.QM]

Jaafar Alomairi, Anne Molitor, Nori Sadouni, Saadat Hussain, Magali Torres, et al.. Integration of high-throughput reporter assays identify a critical enhancer of the Ikzf1 gene. PLoS ONE, 2020, 15 (5), pp.e0233191. ⟨10.1371/journal.pone.0233191⟩. ⟨hal-02773600⟩