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Comprehensive characterization of the embryonic factor LEUTX
Lisa Gawriyski1,2,3, Eeva-Mari Jouhilahti1,3, Masahito Yoshihara4
1Stem Cells and Metabolism Research Program, University of Helsinki, 00290 Helsinki, Finland.
Iscience
|March 6, 2023
Summary
The transcription factor LEUTX is crucial for early human development, activating genes essential for preimplantation embryos. It interacts with histone acetyltransferases to regulate gene expression during this critical stage.
Area of Science:
- Developmental Biology
- Gene Regulation
- Epigenetics
Background:
- LEUTX is a transcription factor expressed in early human embryos (4- to 8-cell stages).
- Its expression is silenced in somatic tissues, suggesting a specific role in early development.
- The precise function of LEUTX in preimplantation development was previously unclear.
Purpose of the Study:
- To comprehensively characterize the function of the LEUTX transcription factor.
- To investigate LEUTX interactions and its role in regulating gene expression during human preimplantation development.
Main Methods:
- Multiomic characterization of LEUTX.
- Utilized two proteomics methods and three genome-wide sequencing approaches.
- Investigated the role of the 9 amino acid transactivation domain (9aaTAD) through mutation analysis.
Main Results:
- LEUTX stably interacts with EP300 and CBP histone acetyltransferases via its 9aaTAD.
- LEUTX targets cis-regulatory sequences overlapping repetitive elements to regulate downstream genes.
- LEUTX acts as a transcriptional activator, upregulating genes like DPPA3 and ZNF280A, crucial for preimplantation development and 8-cell-like markers.
Conclusions:
- LEUTX functions as an enhancer binding protein in preimplantation development.
- LEUTX is a potent transcriptional activator essential for early human embryogenesis.
- The interaction with EP300/CBP and targeting of repetitive elements are key mechanisms for LEUTX function.
