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 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

doi:10.1016/j.isci.2023.106172

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 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

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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 language	English
Article number	106172
Number of pages	29
Journal	iScience
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.isci.2023.106172
Publication status	Published - 17 Mar 2023
MoE publication type	A1 Journal article-refereed

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10.1016/j.isci.2023.106172

1-s2.0-S2589004223002493-mainFinal published version, 3.76 MBLicence: CC BY

https://urn.fi/URN:NBN:fi-fe202402207923

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Gawriyski, L., Jouhilahti, E.-M., Yoshihara, M., Fei, L., Weltner, J., Airenne, T. T., Trokovic, R., Bhagat, S., Tervaniemi, M. H., Murakawa, Y., Salokas, K., Liu, X., Miettinen, S., Bürglin, T. R., Sahu, B., Otonkoski, T., Johnson, M. S., Katayama, S., Varjosalo, M., & Kere, J. (2023). Comprehensive characterization of the embryonic factor LEUTX. iScience, 26(3), Article 106172. https://doi.org/10.1016/j.isci.2023.106172

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title = "Comprehensive characterization of the embryonic factor LEUTX",

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.",

keywords = "Molecular biology, Reproductive medicine, Omics",

author = "Lisa Gawriyski and Eeva-Mari Jouhilahti and Masahito Yoshihara and Liangru Fei and Jere Weltner and Airenne, {Tomi T} and Ras Trokovic and Shruti Bhagat and Tervaniemi, {Mari H} and Yasuhiro Murakawa and Kari Salokas and Xiaonan Liu and Sini Miettinen and B{\"u}rglin, {Thomas R} and Biswajyoti Sahu and Timo Otonkoski and Johnson, {Mark S} and Shintaro Katayama and Markku Varjosalo and Juha Kere",

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year = "2023",

month = mar,

day = "17",

doi = "10.1016/j.isci.2023.106172",

language = "English",

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Gawriyski, L, Jouhilahti, E-M, Yoshihara, M, Fei, L, Weltner, J, Airenne, TT, Trokovic, R, Bhagat, S, Tervaniemi, MH, Murakawa, Y, Salokas, K, Liu, X, Miettinen, S, Bürglin, TR, Sahu, B, Otonkoski, T, Johnson, MS, Katayama, S, Varjosalo, M & Kere, J 2023, 'Comprehensive characterization of the embryonic factor LEUTX', iScience, vol. 26, no. 3, 106172. https://doi.org/10.1016/j.isci.2023.106172

TY - JOUR

T1 - Comprehensive characterization of the embryonic factor LEUTX

AU - Gawriyski, Lisa

AU - Jouhilahti, Eeva-Mari

AU - Yoshihara, Masahito

AU - Fei, Liangru

AU - Weltner, Jere

AU - Airenne, Tomi T

AU - Trokovic, Ras

AU - Bhagat, Shruti

AU - Tervaniemi, Mari H

AU - Murakawa, Yasuhiro

AU - Salokas, Kari

AU - Liu, Xiaonan

AU - Miettinen, Sini

AU - Bürglin, Thomas R

AU - Sahu, Biswajyoti

AU - Otonkoski, Timo

AU - Johnson, Mark S

AU - Katayama, Shintaro

AU - Varjosalo, Markku

AU - Kere, Juha

PY - 2023/3/17

Y1 - 2023/3/17

N2 - 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.

AB - 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.

KW - Molecular biology

KW - Reproductive medicine

KW - Omics

U2 - 10.1016/j.isci.2023.106172

DO - 10.1016/j.isci.2023.106172

M3 - Article

C2 - 36876139

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 3

M1 - 106172

ER -

Comprehensive characterization of the embryonic factor LEUTX

Abstract

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