Multiomics characterisation of LEUTX. LEUTX NET-CAGE

A PAIRED-LIKE homeobox transcription factor LEUTX is expressed in human embryos at the time of embryonic genome activation (EGA); however functions of LEUTX in the context of human EGA are largely unknown. We performed a multiomic characterization of one of these factors, LEUTX, using three genome-wide sequencing approaches and two proteomics methods. Our results show that LEUTX stably interacts with the EP300 and CBP histone acetyltransferases through its 9 amino acid transactivation domain (9aaTAD), as mutation of this domain abolishes the interactions. We show that LEUTX targets a large number of promoters, enhancers, repetitive elements, and regulates the expression of several other transcription and pluripotency factors, as well as hundreds of other genes. Our results support a role for LEUTX as an enhancer binding protein and as an potent transcriptional activator in human embryonic genome activation. These data provide an extensive resource for LEUTX function in human cells.