2026/01/14 by Zicong Zhang, Ilias Georgakopoulos-Soares, Guillaume Bourque +2 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Chromatin Remodeling and Cancer #Genomics and Chromatin Dynamics #Machine Learning in Bioinformatics
paper · pdf · doi:10.1038/s41467-026-68422-3
openalex publication_date 2026/01/14 · openalex created_date 2026/01/15 · openalex updated_date 2026/07/29
Using various biochemical assays that identify transcription factor (TF) binding and histone modifications, cis-regulatory elements (CREs) can be annotated in a genome-wide manner. However, these assays are descriptive and require functional validation. To the best of our knowledge, no technology can simultaneously analyze the regulatory function and epigenomic modifications of a specific sequence. Here, we develop an enrichment followed by epigenomic profiling massively parallel reporter assay (e2MPRA). This technique uses lentivirus to enrich for the integration of specific CREs into the genome and applies MPRA, Cut&Tag or ATAC-seq on them enabling simultaneous, high-throughput analysis of regulatory activity, protein binding, and epigenetic modification. We demonstrate that e2MPRA can dissect the epigenetic functions of TF motifs arranged within synthetic enhancers and evaluate the effects of sequence perturbation on epigenetic states. In summary, e2MPRA advances our understanding of the regulatory code, its effect on the epigenome and how its alteration leads to phenotypic effects.