scholarly journals Transcription factor Mesenchyme Homeobox Protein 2 (MEOX2) modulates nociceptor function

FEBS Journal ◽  
2022 ◽  
Author(s):  
Tomislav Kokotović ◽  
Ewelina M. Lenartowicz ◽  
Michiel Langeslag ◽  
Cosmin I. Ciotu ◽  
Christopher W. Fell ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Homeobox Protein

GHF-1, a Tissue-Specific Transcription Factor, is a Homeobox Protein

1989 ◽  
pp. 90-109
Author(s):  
José-Luis Castrillo ◽  
Lars E. Theill ◽  
Mordechai Bodner ◽  
Michael Karin
Keyword(s):  
Transcription Factor ◽  
Tissue Specific ◽  
Specific Transcription Factor ◽  
Homeobox Protein

scholarly journals DUX4 Signalling in the Pathogenesis of Facioscapulohumeral Muscular Dystrophy

2020 ◽  
Vol 21 (3) ◽  
pp. 729 ◽  
Author(s):  
Kenji Rowel Q. Lim ◽  
Quynh Nguyen ◽  
Toshifumi Yokota
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Transcription Factor ◽  
Muscular Dystrophy ◽  
Embryonic Development ◽  
Disease Onset ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Signalling Pathways ◽  
Progressive Muscle Weakness ◽  
Homeobox Protein

Facioscapulohumeral muscular dystrophy (FSHD) is a disabling inherited muscular disorder characterized by asymmetric, progressive muscle weakness and degeneration. Patients display widely variable disease onset and severity, and sometimes present with extra-muscular symptoms. There is a consensus that FSHD is caused by the aberrant production of the double homeobox protein 4 (DUX4) transcription factor in skeletal muscle. DUX4 is normally expressed during early embryonic development, and is then effectively silenced in all tissues except the testis and thymus. Its reactivation in skeletal muscle disrupts numerous signalling pathways that mostly converge on cell death. Here, we review studies on DUX4-affected pathways in skeletal muscle and provide insights into how understanding these could help explain the unique pathogenesis of FSHD.

scholarly journals The transcription factor prospero homeobox protein 1 is a direct target of SoxC proteins during developmental vertebrate neurogenesis

2018 ◽  
Vol 146 (3) ◽  
pp. 251-268 ◽  
Author(s):  
Anne Jacob ◽  
Hannah M. Wüst ◽  
Johannes M. Thalhammer ◽  
Franziska Fröb ◽  
Melanie Küspert ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Homeobox Protein ◽  
Direct Target

scholarly journals In silico analysis of transcription factor binding sites in promoters of germin-like protein genes in rice

2016 ◽  
Vol 68 (4) ◽  
pp. 863-876 ◽  
Author(s):  
Muhammad Ilyas ◽  
Syed Naqvi ◽  
Tariq Mahmood
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
In Silico ◽  
In Silico Analysis ◽  
Chromosome 8 ◽  
Upstream Region ◽  
Asian Rice ◽  
Homeobox Protein ◽  
Annotation Project ◽  
Tata Box Binding Protein

Germins (GERs) and germin-like proteins (GLPs) play important roles in responses to various stresses; however, their function is still not fully understood. Significant insight into their function can be obtained by analyzing their promoters. In the present study, the 5' upstream promoters (1000 bp) of 43 Asian rice (Oryza sativa var. Japonica) GLP genes were retrieved from the Plant Ensemble, based on the Rice Annotation Project database (RAP-DB). Phylogenetic analysis via MEGA6 showed a narrow genetic background (0.2%) with a Tajima neutrality value (?) of 0.69. Overall, 4234 transcription factor (TF) binding sites (TFBSs) were found on chromosomes 1, 2, 3, 4, 5, 8, 9, 11 and 12 via ?MatInspector? from 90 different TF families using a total of 444 families. Common TFs and DiAlign analyses showed that arabidopsis homeobox protein (AHBP), MYB-like proteins (MYBL) and vertebrate TATA-box-binding protein (VTBP) were the most abundant, common and evolutionarily conserved elements in the upstream region from 0 to -800. Finding their mutual interaction via Farmworker analysis uncovered three new cisregulatory modules (VTBP_VTBP, MYBS_MYBS, and AHBP_VTBP), which appear to be decisive for OsGLP regulation. In silico functional analysis via ModelInspector revealed 77 cis-regulatory modules, each comprised of two elements, among which DOFF_OPAQ_03 and GTBX_MYCL_01 were the most frequent and mostly found on chromosome 8 and 12, indicating that the combinatorial interaction of these elements has a fundamental role in various biological processes. The study revealed the importance of these elements in regulating OsGLP expression that will help in predicting the role of these genes in various stresses, and can have application in biotechnology.

scholarly journals Transcriptional regulation of a mouse Clara cell-specific protein (mCC10) gene by the NKx transcription factor family members thyroid transciption factor 1 and cardiac muscle-specific homeobox protein (CSX).

1996 ◽  
Vol 16 (5) ◽  
pp. 2056-2064 ◽  
Author(s):  
M K Ray ◽  
C Y Chen ◽  
R J Schwartz ◽  
F J DeMayo
Keyword(s):  
Transcription Factor ◽  
Cardiac Muscle ◽  
Binding Site ◽  
Binding Sites ◽  
Promoter Region ◽  
Target Genes ◽  
Clara Cell ◽  
Proximal Promoter ◽  
Growth Hormone Gene ◽  
Homeobox Protein

This report defines the elements between bp -800 and -166 that regulate the quantitative level of mouse CC10 (mCC10) transcription in the lungs. The elements in this promoter domain are the response elements for the NKx2.1 homeobox protein, thyroid transcription factor 1 (TTF1). DNase I footprint analysis identified five binding sites for TTF1 between bp -800 and - 166. These sites are located at bp -344 to -335, - 282 to -273, -268 to -263, -258 to -249, and - 199 to - 190. In addition to these enhancer elements, two TTF1 binding sites were identified in the proximal promoter region (bp - 166 to + 1), at bp -74 to -69 and -49 to -39. An identical footprint of the mCC10 promoter region was also observed with another member of the NKx family, NKx 2.5, the cardiac muscle-specific homeobox protein (CSX). Deletion and linker-scanner mutational analyses of the TTF1 binding sites in the mCC10 distal promoter region with transient cotransfection into CV1 cells with either TTF1 or CSX identified the site located between bp -282 and -273 as the major regulator of CC10 expression, with minor regulation by sites at bp -344 to -335 and -258 to -249. The importance of the NKx binding site at bp -282 to -273 was verified in vivo. Transgenic mice generated with the human growth hormone gene fused to 800 bp of the mCC10 promoter containing a mutation in the TTF1 binding site at bp -282 to -273 showed a reduction in transgene expression equal to that of the mice generated with only 166 bp of 5'-flanking DNA. This report emphasizes the importance of TTF1 or related factors as major regulators of pulmonary gene expression and demonstrates the potential of NKx proteins to bind and activate heterologous target genes.

scholarly journals Gamete fusion rapidly reconstitutes a bi-partite transcription factor to block re-fertilization

2018 ◽  
Author(s):  
Aleksandar Vještica ◽  
Laura Merlini ◽  
Pedro N’kosi ◽  
Sophie G Martin
Keyword(s):  
Transcription Factor ◽  
Sexual Reproduction ◽  
Model Organism ◽  
Nuclear Accumulation ◽  
M Cell ◽  
Cell Fates ◽  
Gamete Fusion ◽  
Zygotic Transcription ◽  
Distinct Cell ◽  
Homeobox Protein

AbstractThe ploidy cycle, integral to sexual reproduction, requires not only meiosis to halve the number of chromosomes, but also mechanisms that ensure zygotes are formed by exactly two partners1–5. During sexual reproduction of the fungal model organism Schizosaccharomyces pombe, haploid P- and M-cells normally fuse to form a diploid zygote that immediately enters meiosis6. Here, we reveal that fast post-fusion reconstitution of a bi-partite transcription factor actively blocks re-fertilization. We first identify mutants that undergo transient cell fusion involving cytosol exchange but not karyogamy, and show this drives distinct cell fates in the two gametes: The P-partner undergoes lethal, haploid meiosis while the M-cell persists in mating. Consistently, we find that the zygotic transcription that drives meiosis is initiated rapidly only from the P-parental genome, even in wild type cells. This asymmetric gene expression depends on a bi-partite complex formed post-fusion between the nuclear P-cell-specific homeobox protein Pi and a cytosolic M-specific peptide Mi7,8, which is captured by Pi in the P-nucleus. Zygotic transcription is thus poised to initiate in the P-nucleus as fast as Mi reaches it. The asymmetric nuclear accumulation is inherent to the transcription factor design, and is reconstituted by a pair of synthetic interactors, one localized to the nucleus of one gamete and the other in the cytosol of its partner. Strikingly, imposing a delay in zygotic transcription, by postponing Mi expression or deleting its transcriptional target in the P-genome, leads to zygotes fusing with additional gametes, thus forming polyploids and eventually aneuploid progeny. We further show that the signaling cascade to block re-fertilization shares components with, but bifurcates from, meiotic induction9–11. Thus, cytoplasmic connection upon gamete fusion leads to rapid reconstitution of a bi-partite transcription factor in one partner to block re-fertilization and induce meiosis, thus ensuring genome maintenance during sexual reproduction.

Mezzo, apaired-likehomeobox protein is an immediate target of Nodal signalling and regulates endoderm specification in zebrafish

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 4901-4914 ◽  
Author(s):  
Morgane Poulain ◽  
Thierry Lepage
Keyword(s):  
Transcription Factor ◽  
Marker Gene ◽  
Ectopic Expression ◽  
Signalling Pathway ◽  
Turn On ◽  
Zygotic Transcription ◽  
Homeobox Protein ◽  
Morpholino Oligonucleotides ◽  
Antisense Morpholino Oligonucleotides ◽  
Antisense Morpholino

Endoderm specification in zebrafish is mediated by the zygotic transcription factors Bon/Mixer, Faust/Gata5, Casanova and Sox17, whose expression is induced by Nodal signalling. Bon/Mixer and Gata5 require Casanova in order to promote endoderm formation and all three factors act upstream of sox17, but it is not clear whether Casanova acts downstream of or in parallel to Bon/Mixer and Gata5. An additional factor induced at the margin of the blastoderm by Nodal signalling is thought to be required to induce casanova expression. We show that Mezzo, a novelpaired-like homeobox protein, may be this missing transcription factor. The homeobox of Mezzo is mostly related to the homeodomain of the Mix-like and Mixer homeoproteins, but Mezzo is distinct from Bon/Mixer, the product of the bonnie and clyde gene. Like bon/mixer, mezzois expressed transiently in mesendoderm precursors. By analysing the expression of mezzo in various mutants of Nodal signalling, we show that its expression strictly depends on a functional Nodal signalling pathway. By expressing a constitutively active Nodal receptor in the presence of translation inhibitors, we further demonstrate that mezzo, bonnie and clyde, and casanova are all immediate early targets of Nodal signalling, while sox17 requires post-MBT protein synthesis in order to be induced. Overexpression of mezzo mRNA can induce ectopic expression of casanova and sox17 and can also turn on the pan mesodermal marker gene ntl. We show that the function ofmezzo is redundant with that of bonnie and clyde and thatmezzo RNA can partially rescue bonnie and clyde mutants. Injection of antisense Morpholino oligonucleotides targeted againstmezzo into bonnie and clyde mutant embryos abolishes allsox17 expression and aggravates their mutant phenotype. These results highlight the complexity of the transcriptional network operating during endoderm formation. They place mezzo as a new transcription factor with unique properties acting in parallel with bonnie and clyde,faust and casanova in the Nodal signalling pathway that controls specification of mesoderm and endoderm in zebrafish.

scholarly journals Identification and validation of the phosphorylation sites on Aristaless-related homeobox protein

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Xiuyu Shi ◽  
Wenbo Lin ◽  
Xiang Gao ◽  
Wen Xie ◽  
Jeffrey A. Golden ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Cyclin D1 ◽  
Nuclear Localization ◽  
Transcriptional Activator ◽  
Phosphorylation Sites ◽  
Mechanistic Insight ◽  
Homeobox Protein ◽  
Repressor Activity

Abstract The Aristaless-related homeobox protein (ARX) is a transcription factor expressed in the developing forebrain, skeletal muscle, pancreas, testis, and a variety of other tissues. It is known to have context-dependent transcriptional activator and repressor activity, although how it can achieve these opposing functions remains poorly understood. We hypothesized phosphorylation status might play a role in pivoting ARX between functioning as an activator or repressor. To gain further mechanistic insight as to how ARX functions, we identified multiple phosphorylation sites on ARX. We further established PKA as the kinase that phosphorylates ARX at least at Ser266 in mice. Two other kinases, CK2α and CDK4/cyclin D1, were also identified as kinases that phosphorylate ARX in vitro. Unexpectedly, phosphorylation status did not change either the nuclear localization or transcriptional function of ARX.

scholarly journals Identification of Novel Candidate Genes Implicated in Odontogenic Potential in the Developing Mouse Tooth Germ using Transcriptome Analysis

2021 ◽  
Author(s):  
Yeo-Kyeong Shin ◽  
Seongmin Cheon ◽  
Sung-Duk Kim ◽  
Jung-Sun Moon ◽  
Jae-Young Kim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Developmental Stages ◽  
Tooth Development ◽  
Tooth Germ ◽  
Molar Tooth ◽  
Gene Enhancer ◽  
Transcription Factor Genes ◽  
Homeobox Protein ◽  
New Perspective ◽  
Whole Transcriptome

Abstract In tooth bioengineering for replacement therapy of missing teeth, the utilized cells must possess an inductive signal-forming ability to initiate odontogenesis. This ability is called odontogenic potential. In mice, the odontogenic potential signal is known to be translocated from the epithelium to the mesenchyme at the early bud stage in the developing molar tooth germ. However, the identity of the molecular constituents of this process remains unclear. Therefore, in this study, whole transcriptome profiles of the mouse molar tooth germ epithelium and mesenchyme were investigated using the RNA sequencing (RNA-seq) technique. The analyzed transcriptomes corresponded to two developmental stages, embryonic day 11.5 (E11.5) and 14.5 (E14.5), which represent the odontogenic potential shifts. We identified differentially expressed genes (DEGs), which were specifically overexpressed in both the E11.5 epithelium and E14.5 mesenchyme, but not expressed in their respective counterparts. Of the fifty-five DEGs identified, the top three most expressed transcription factor genes (transcription factor AP-2 beta isoform 3 [TFAP2B], developing brain homeobox protein 2 [DBX2], and insulin gene enhancer protein ISL-1 [ISL1]) and three tooth development-related genes (transcription factor HES-5 [HES5], platelet-derived growth factor D precursor [PDGFD], semaphrin-3A precursor [SEMA3A]) were selected and validated by quantitative RT-PCR. Using immunofluorescence staining, the TFAP2B protein expression was found to be localized only at the E11.5 epithelium and E14.5 mesenchyme. Thus, our empirical findings in the present study may provide a new perspective into the characterization of the molecules responsible for the odontogenic potential and may have an implication in the cell-based whole tooth regeneration strategy.

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