Comprehensive characterization of the embryonic factor LEUTX

Lisa Gawriyski, Eeva-Mari Jouhilahti, Masahito Yoshihara, Liangru Fei, Jere Weltner, Tomi Airenne, Shruti Bhagat, Ras Trokovic, Mari H. 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

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
Article number106172
JournaliScience
Volume26
Issue number3
Number of pages30
ISSN2589-0042
DOIs
Publication statusPublished - 17 Mar 2023
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology

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