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},
  author={Shintaro Katayama and Vipin Ranga and Eeva-Mari Jouhilahti and Tomi T Airenne and Mark S. Johnson and Krishanu Mukherjee and Thomas R. B{\"u}rglin and Juha Kere},
  journal={Scientific Reports},
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… 
PRD-Class Homeobox Genes in Bovine Early Embryos: Function, Evolution, and Overlapping Roles
Evidence is found that bovine ARGFX and LEUTX have overlapping functions, in contrast to their antagonistic roles in humans, and the hypothesis of functional overlap between ETCH box genes within a species, roles for ETCHbox genes in blastocyst formation and the change of their functions over evolutionary time is supported.
Dynamic Molecular Evolution of Mammalian Homeobox Genes: Duplication, Loss, Divergence and Gene Conversion Sculpt PRD Class Repertoires
Comparisons of ETCHbox genes of 34 mammalian species reveal dynamic patterns of gene loss and tandem duplication, including the presence of a large tandem array of LEUTX loci in the genome of the European rabbit (Oryctolagus cuniculus).
Relationship of DUX4 and target gene expression in FSHD myocytes
A unique DUX4 expression pattern and its relationship to the expression of target genes, and evidence for self-sustainability of the target gene network are revealed and provide important new insights into the FSHD disease mechanism.
Therapy-related Myeloid Leukemia With the Translocation t(8;19)(p11;q13) Leading to a KAT6A-LEUTX Fusion Gene
The present case is the second therapy-related AML, and the third AML overall, in which both a t(8;19)(p11;q13) and its molecular result, a KAT6A-LEUTX fusion gene, are described, which deregulates transcription and induces leukemogenesis.
Muscle group specific transcriptomic and DNA methylation differences related to developmental patterning in FSHD
It is found that TA and quadricep retain methylation and expression differences in transcription factors that are key to muscle group specification during embryogenesis, which may contribute to susceptibility in FSHD.
DUX4 regulates oocyte to embryo transition in human
It is concluded that DUX4 is a pioneering factor that regulates human oocyte to embryo transition through regulating oocyte mRNA degradation, as well as direct binding and activation of minor genome activation genes, and genomic repeat elements.
A novel BRD4‐LEUTX fusion in a pediatric sarcoma with epithelioid morphology and diffuse S100 expression
A case of a 10‐year‐old girl with an epithelioid malignancy of the orbit is described, and a novel in‐frame BRD4‐LEUTX fusion gene is revealed, indicating that BRD 4‐LEutX fusion leads to LEUTX re‐activation.


The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation
Using a human embryonic stem cell overexpression model, it is shown that the complete homeodomain isoform is functional and sufficient to activate the transcription of a large proportion of the genes that are upregulated in human embryo genome activation (EGA).
Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammals
It is concluded that a dynamic chromosome region spawned a set of evolutionarily new homeobox genes, the ETCHbox genes, specifically in eutherian mammals, which permitted fine-tuning of cell fate decisions necessary for specification and function of embryonic and extra-embryonic tissues utilised in mammalian development and pregnancy.
Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos
The data implicate a role for these previously uncharacterized PRD-like homeodomain proteins in the regulation of human embryo genome activation and preimplantation embryo development.
The dynamics of vertebrate homeobox gene evolution: gain and loss of genes in mouse and human lineages
There has been much more homeobox gene loss in the rodent evolutionary lineage than in the primate lineage, and a step towards relating genomic evolution to phenotypic evolution is taken.
Evolution of homeobox genes
  • P. Holland
  • Biology
    Wiley interdisciplinary reviews. Developmental biology
  • 2013
Genomic data suggest that the ANTP class diversified by extensive tandem duplication to generate a large array of genes, including an NK gene cluster and a hypothetical ProtoHox gene cluster that duplicated to generate Hox and ParaHox genes.
Homeodomain subtypes and functional diversity.
Homeobox genes perform key roles for all aspects of the development of an organism, and several particular types of homeodomain proteins play roles in the determination of cell fates and cell differentiation.
Novel PRD-like homeodomain transcription factors and retrotransposon elements in early human development
High-resolution RNA sequencing of 348 oocytes, zygotes and single blastomeres from 2- to 3-day-old embryos provides a detailed analysis of the human preimplantation transcriptome and identifies significantly enriched gene regulatory motifs that often overlap with Alu elements.
Mouse Obox and Crxos modulate preimplantation transcriptional profiles revealing similarity between paralogous mouse and human homeobox genes
Mouse Crxos and human ARGFX homeobox genes are paralogous rather than orthologous, yet they have evolved to regulate a common set of genes, suggesting there was compensation of function alongside gene loss through co-option of a different locus.
Diversity of human and mouse homeobox gene expression in development and adult tissues
The identification of a set of eutherian-specific homeobox genes peaking from human 8-cell to morula stages suggests co-option of new genes to new developmental roles in evolution and is compared to an evolutionarily-based classification.
In Vivo Mutational Analysis of the DNA Binding Domain of the Tissue-specific Transcription Factor, Pit-1 (*)
An approach involving random, in vitro mutagenesis followed by functional screening in Saccharomyces cerevisiae identified a number of point mutations that altered the function of the Pit-1 DNA binding domain.