Cargando…

Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis

Recently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human embryogenesis is still subject to debate. We confirmed that human...

Descripción completa

Detalles Bibliográficos
Autores principales: Katayama, Shintaro, Ranga, Vipin, Jouhilahti, Eeva-Mari, Airenne, Tomi T., Johnson, Mark S., Mukherjee, Krishanu, Bürglin, Thomas R., Kere, Juha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258689/
https://www.ncbi.nlm.nih.gov/pubmed/30479355
http://dx.doi.org/10.1038/s41598-018-35547-5
_version_ 1783374535449378816
author Katayama, Shintaro
Ranga, Vipin
Jouhilahti, Eeva-Mari
Airenne, Tomi T.
Johnson, Mark S.
Mukherjee, Krishanu
Bürglin, Thomas R.
Kere, Juha
author_facet Katayama, Shintaro
Ranga, Vipin
Jouhilahti, Eeva-Mari
Airenne, Tomi T.
Johnson, Mark S.
Mukherjee, Krishanu
Bürglin, Thomas R.
Kere, Juha
author_sort Katayama, Shintaro
collection PubMed
description Recently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human embryogenesis is still subject to debate. We confirmed that human LEUTX acts as a TAATCC-targeting transcriptional activator, like other K50-type PAIRED-LIKE TFs. Phylogenetic comparisons revealed that Leutx proteins are conserved across Placentalia and comprise two conserved domains, the homeodomain, and a Leutx-specific domain containing putative transcriptional activation motifs (9aaTAD). Examination of human genotype resources revealed 116 allelic variants in LEUTX. Twenty-four variants potentially affect function, but they occur only heterozygously at low frequency. One variant affects a DNA-specificity determining residue, mutationally reachable by a one-base transition. In vitro and in silico experiments showed that this LEUTX mutation (alanine to valine at position 54 in the homeodomain) results in a transactivational loss-of-function to a minimal TAATCC-containing promoter and a 36 bp motif enriched in genes involved in embryo genome activation. A compensatory change in residue 47 restores function. The results support the notion that human LEUTX functions as a transcriptional activator important for human embryogenesis.
format Online
Article
Text
id pubmed-6258689
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-62586892018-12-03 Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis Katayama, Shintaro Ranga, Vipin Jouhilahti, Eeva-Mari Airenne, Tomi T. Johnson, Mark S. Mukherjee, Krishanu Bürglin, Thomas R. Kere, Juha Sci Rep Article Recently, human PAIRED-LIKE homeobox transcription factor (TF) genes were discovered whose expression is limited to the period of embryo genome activation up to the 8-cell stage. One of these TFs is LEUTX, but its importance for human embryogenesis is still subject to debate. We confirmed that human LEUTX acts as a TAATCC-targeting transcriptional activator, like other K50-type PAIRED-LIKE TFs. Phylogenetic comparisons revealed that Leutx proteins are conserved across Placentalia and comprise two conserved domains, the homeodomain, and a Leutx-specific domain containing putative transcriptional activation motifs (9aaTAD). Examination of human genotype resources revealed 116 allelic variants in LEUTX. Twenty-four variants potentially affect function, but they occur only heterozygously at low frequency. One variant affects a DNA-specificity determining residue, mutationally reachable by a one-base transition. In vitro and in silico experiments showed that this LEUTX mutation (alanine to valine at position 54 in the homeodomain) results in a transactivational loss-of-function to a minimal TAATCC-containing promoter and a 36 bp motif enriched in genes involved in embryo genome activation. A compensatory change in residue 47 restores function. The results support the notion that human LEUTX functions as a transcriptional activator important for human embryogenesis. Nature Publishing Group UK 2018-11-27 /pmc/articles/PMC6258689/ /pubmed/30479355 http://dx.doi.org/10.1038/s41598-018-35547-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Katayama, Shintaro
Ranga, Vipin
Jouhilahti, Eeva-Mari
Airenne, Tomi T.
Johnson, Mark S.
Mukherjee, Krishanu
Bürglin, Thomas R.
Kere, Juha
Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis
title Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis
title_full Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis
title_fullStr Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis
title_full_unstemmed Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis
title_short Phylogenetic and mutational analyses of human LEUTX, a homeobox gene implicated in embryogenesis
title_sort phylogenetic and mutational analyses of human leutx, a homeobox gene implicated in embryogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258689/
https://www.ncbi.nlm.nih.gov/pubmed/30479355
http://dx.doi.org/10.1038/s41598-018-35547-5
work_keys_str_mv AT katayamashintaro phylogeneticandmutationalanalysesofhumanleutxahomeoboxgeneimplicatedinembryogenesis
AT rangavipin phylogeneticandmutationalanalysesofhumanleutxahomeoboxgeneimplicatedinembryogenesis
AT jouhilahtieevamari phylogeneticandmutationalanalysesofhumanleutxahomeoboxgeneimplicatedinembryogenesis
AT airennetomit phylogeneticandmutationalanalysesofhumanleutxahomeoboxgeneimplicatedinembryogenesis
AT johnsonmarks phylogeneticandmutationalanalysesofhumanleutxahomeoboxgeneimplicatedinembryogenesis
AT mukherjeekrishanu phylogeneticandmutationalanalysesofhumanleutxahomeoboxgeneimplicatedinembryogenesis
AT burglinthomasr phylogeneticandmutationalanalysesofhumanleutxahomeoboxgeneimplicatedinembryogenesis
AT kerejuha phylogeneticandmutationalanalysesofhumanleutxahomeoboxgeneimplicatedinembryogenesis