Comprehensive characterization of the embryonic factor LEUTX
Lisa Gawriyski, Eeva‐Mari Jouhilahti, Masahito Yoshihara, Liangru Fei, Jere Weltner, Tomi T. Airenne, Ras Trokovic, Shruti Bhagat, Mari Tervaniemi, Yasuhiro Murakawa, Kari Salokas, Xiaonan Liu, Sini Miettinen, Thomas R. Bürglin, Biswajyoti Sahu, Timo Otonkoski, Mark S. Johnson, Shintaro Katayama, Markku Varjosalo, Juha Kere
Abstract
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.