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

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 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 journal › Article › Scientific › peer-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 language	English
Article number	106172
Journal	iScience
Volume	26
Issue number	3
Number of pages	30
ISSN	2589-0042
DOIs	https://doi.org/10.1016/j.isci.2023.106172
Publication status	Published - 17 Mar 2023
MoE publication type	A1 Journal article-refereed

Fields of Science

1182 Biochemistry, cell and molecular biology

Access to Document

10.1016/j.isci.2023.106172

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

Cite this

Gawriyski, L., Jouhilahti, E.-M., Yoshihara, M., Fei, L., Weltner, J., Airenne, T., Bhagat, S., Trokovic, R., 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

@article{862d3f1b31594163ae20cd824da4fc1f,

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 = "1182 Biochemistry, cell and molecular biology",

author = "Lisa Gawriyski and Eeva-Mari Jouhilahti and Masahito Yoshihara and Liangru Fei and Jere Weltner and Tomi Airenne and Shruti Bhagat and Ras Trokovic 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",

year = "2023",

month = mar,

day = "17",

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

language = "English",

volume = "26",

journal = "iScience",

issn = "2589-0042",

publisher = "Cell Press Elsevier Inc.",

number = "3",

}

Gawriyski, L, Jouhilahti, E-M, Yoshihara, M, Fei, L, Weltner, J, Airenne, T, Bhagat, S, Trokovic, R, 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

AU - Bhagat, Shruti

AU - Trokovic, Ras

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 - 1182 Biochemistry, cell and molecular biology

U2 - 10.1016/j.isci.2023.106172

DO - 10.1016/j.isci.2023.106172

M3 - Article

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 3

M1 - 106172

ER -