Comprehensive characterization of the embryonic factor LEUTX

The paired-like homeobox transcription factor LEUTX is expressed in human preimplantation embryos between the 4-and 8-cell stages, and then silenced in somatic tissues. To characterize the function of LEUTX, we performed a multiomic characterization of LEUTX using two proteomics methods and three genome-wide sequencing approaches. 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. LEUTX targets genomic cis-regulatory sequences that overlap with repetitive elements, and through these elements it is suggested to regulate the expression of its downstream genes. We find LEUTX to be a transcriptional activator, upregulating several genes linked to preimplantation development as well as 8-cell-like markers, such as DPPA3 and ZNF280A. Our results support a role for LEUTX in preimplantation development as an enhancer binding protein and as a potent transcriptional activator.

Automated summary

LEUTX, a transcription factor, is expressed in human preimplantation embryos at the 4-8 cell stages and silenced in somatic tissues. Through multiomic characterization, we found that LEUTX interacts with histone acetyltransferases, EP300 and CBP, via its 9 amino acid transactivation domain. It targets genomic cis-regulatory sequences overlapping with repetitive elements and functions as a transcriptional activator, upregulating genes involved in preimplantation development and 8-cell-like markers.