scholarly journals Hox Proteins in the Regulation of Muscle Development

2021 ◽  
Vol 9 ◽  
Author(s):  
Gabriela Poliacikova ◽  
Corinne Maurel-Zaffran ◽  
Yacine Graba ◽  
Andrew J. Saurin
Keyword(s):  
Protein Function ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Hox Genes ◽  
Fruit Fly ◽  
Comprehensive Overview ◽  
Hox Proteins ◽  
Vertebrate Muscle ◽  
Hox Protein ◽  
Vertebrate Skeleton

Hox genes encode evolutionary conserved transcription factors that specify the anterior–posterior axis in all bilaterians. Being well known for their role in patterning ectoderm-derivatives, such as CNS and spinal cord, Hox protein function is also crucial in mesodermal patterning. While well described in the case of the vertebrate skeleton, much less is known about Hox functions in the development of different muscle types. In contrast to vertebrates however, studies in the fruit fly, Drosophila melanogaster, have provided precious insights into the requirement of Hox at multiple stages of the myogenic process. Here, we provide a comprehensive overview of Hox protein function in Drosophila and vertebrate muscle development, with a focus on the molecular mechanisms underlying target gene regulation in this process. Emphasizing a tight ectoderm/mesoderm cross talk for proper locomotion, we discuss shared principles between CNS and muscle lineage specification and the emerging role of Hox in neuromuscular circuit establishment.

egl-27 generates anteroposterior patterns of cell fusion in C. elegans by regulating Hox gene expression and Hox protein function

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3303-3312 ◽  
Author(s):  
Q. Ch'ng ◽  
C. Kenyon
Keyword(s):  
Gene Expression ◽  
Cell Fusion ◽  
Protein Function ◽  
Hox Genes ◽  
Positional Information ◽  
Cell Fates ◽  
Hox Proteins ◽  
Hox Gene ◽  
C Elegans ◽  
Hox Protein

Hox genes pattern the fates of the ventral ectodermal Pn.p cells that lie along the anteroposterior (A/P) body axis of C. elegans. In these cells, the Hox genes are expressed in sequential overlapping domains where they control the ability of each Pn.p cell to fuse with the surrounding syncytial epidermis. The activities of Hox proteins are sex-specific in this tissue, resulting in sex-specific patterns of cell fusion: in hermaphrodites, the mid-body cells remain unfused, whereas in males, alternating domains of syncytial and unfused cells develop. We have found that the gene egl-27, which encodes a C. elegans homologue of a chromatin regulatory factor, specifies these patterns by regulating both Hox gene expression and Hox protein function. In egl-27 mutants, the expression domains of Hox genes in these cells are shifted posteriorly, suggesting that egl-27 influences A/P positional information. In addition, egl-27 controls Hox protein function in the Pn.p cells in two ways: in hermaphrodites it inhibits MAB-5 activity, whereas in males it permits a combinatorial interaction between LIN-39 and MAB-5. Thus, by selectively modifying the activities of Hox proteins, egl-27 elaborates a simple Hox expression pattern into complex patterns of cell fates. Taken together, these results implicate egl-27 in the diversification of cell fates along the A/P axis and suggest that chromatin reorganization is necessary for controlling Hox gene expression and Hox protein function.

scholarly journals Hox dosage contributes to flight appendage morphology in Drosophila

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rachel Paul ◽  
Guillaume Giraud ◽  
Katrin Domsch ◽  
Marilyne Duffraisse ◽  
Frédéric Marmigère ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Differential Expression ◽  
Hox Genes ◽  
Expression Profiles ◽  
Fruit Fly ◽  
Insect Species ◽  
Wing Morphology ◽  
Hox Proteins ◽  
Spatial Expression ◽  
Flying Insects

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.

scholarly journals The HOX Homeodomain Proteins Block CBP Histone Acetyltransferase Activity

2001 ◽  
Vol 21 (21) ◽  
pp. 7509-7522 ◽  
Author(s):  
Wei-fang Shen ◽  
Keerthi Krishnan ◽  
H. J. Lawrence ◽  
Corey Largman
Keyword(s):  
Dna Binding ◽  
Protein Function ◽  
Histone Acetyltransferase ◽  
Gene Activation ◽  
Homeodomain Proteins ◽  
Hox Proteins ◽  
Reporter Assays ◽  
Hox Protein

ABSTRACT Despite the identification of PBC proteins as cofactors that provide DNA affinity and binding specificity for the HOX homeodomain proteins, HOX proteins do not demonstrate robust activity in transient-transcription assays and few authentic downstream targets have been identified for these putative transcription factors. During a search for additional cofactors, we established that each of the 14 HOX proteins tested, from 11 separate paralog groups, binds to CBP or p300. All six isolated homeodomain fragments tested bind to CBP, suggesting that the homeodomain is a common site of interaction. Surprisingly, CBP-p300 does not form DNA binding complexes with the HOX proteins but instead prevents their binding to DNA. The HOX proteins are not substrates for CBP histone acetyltransferase (HAT) but instead inhibit the activity of CBP in both in vitro and in vivo systems. These mutually inhibitory interactions are reflected by the inability of CBP to potentiate the low levels of gene activation induced by HOX proteins in a range of reporter assays. We propose two models for HOX protein function: (i) HOX proteins may function without CBP HAT to regulate transcription as cooperative DNA binding molecules with PBX, MEIS, or other cofactors, and (ii) the HOX proteins may inhibit CBP HAT activity and thus function as repressors of gene transcription.

scholarly journals Developmental Robustness: The Haltere Case in Drosophila

2021 ◽  
Vol 9 ◽  
Author(s):  
Guillaume Giraud ◽  
Rachel Paul ◽  
Marilyne Duffraisse ◽  
Soumen Khan ◽  
L. S. Shashidhara ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Mode Of Action ◽  
Molecular Model ◽  
Fruit Fly ◽  
Hox Proteins ◽  
Hox Gene ◽  
Environmental Variations ◽  
Hox Protein ◽  
Independent Mode ◽  
High Expression Level

Developmental processes have to be robust but also flexible enough to respond to genetic and environmental variations. Different mechanisms have been described to explain the apparent antagonistic nature of developmental robustness and plasticity. Here, we present a “self-sufficient” molecular model to explain the development of a particular flight organ that is under the control of the Hox gene Ultrabithorax (Ubx) in the fruit fly Drosophila melanogaster. Our model is based on a candidate RNAi screen and additional genetic analyses that all converge to an autonomous and cofactor-independent mode of action for Ubx. We postulate that this self-sufficient molecular mechanism is possible due to an unusually high expression level of the Hox protein. We propose that high dosage could constitute a so far poorly investigated molecular strategy for allowing Hox proteins to both innovate and stabilize new forms during evolution.

scholarly journals Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Xiao Jin ◽  
Lu Dai ◽  
lan Yi Ma ◽  
yan Jia Wang ◽  
hao Hai Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Tumour Size ◽  
Therapeutic Targets ◽  
Cochrane Library ◽  
Clinical Value ◽  
Hox Proteins ◽  
Aberrant Expression ◽  
Hox Protein

Abstract Background: An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and action mechanisms of HOX proteins in GC. Methods: A comprehensive search of PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX protein expression on the prognosis and clinicopathological features of GC, respectively. Results: Nineteen studies containing 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I2=90.5%, p=0.000). According to the subgroup analysis, increased expression of HOX protein in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36-0.59, I2=3.1%, p=0.377), while overexpression of HOX protein in the upregulated subgroup was correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79-3.74, I2=73.5%, p=0.000). The aberrant expression of HOX protein was crucially related to the TNM stage, depth of tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC. In addition, the molecular mechanisms by which HOX proteins regulate tumorigenesis and development of GC were also explored. Conclusions: HOX proteins play vital roles in GC progression, which might serve as prognostic markers and therapeutic targets for GC.

scholarly journals Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid

Development ◽  
2020 ◽  
Vol 148 (1) ◽  
pp. dev193813
Author(s):  
Alejandra C. López-Delgado ◽  
Irene Delgado ◽  
Vanessa Cadenas ◽  
Fátima Sánchez-Cabo ◽  
Miguel Torres
Keyword(s):  
Transcription Factors ◽  
Retinoic Acid ◽  
Hox Genes ◽  
Feedback Regulation ◽  
Axial Skeleton ◽  
Paraxial Mesoderm ◽  
Hox Proteins ◽  
Skeletal Defects ◽  
Hox Protein ◽  
Anterior Posterior

ABSTRACTVertebrate axial skeletal patterning is controlled by co-linear expression of Hox genes and axial level-dependent activity of HOX protein combinations. MEIS transcription factors act as co-factors of HOX proteins and profusely bind to Hox complex DNA; however, their roles in mammalian axial patterning remain unknown. Retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors; however, whether this role is related to MEIS/HOX activity remains unknown. Here, we study the role of Meis in axial skeleton formation and its relationship to the RA pathway in mice. Meis elimination in the paraxial mesoderm produces anterior homeotic transformations and rib mis-patterning associated to alterations of the hypaxial myotome. Although Raldh2 and Meis positively regulate each other, Raldh2 elimination largely recapitulates the defects associated with Meis deficiency, and Meis overexpression rescues the axial skeletal defects in Raldh2 mutants. We propose a Meis-RA-positive feedback loop, the output of which is Meis levels, that is essential to establish anterior-posterior identities and patterning of the vertebrate axial skeleton.

Hox repression of a target gene: extradenticle-independent, additive action through multiple monomer binding sites

Development ◽  
2002 ◽  
Vol 129 (13) ◽  
pp. 3115-3126 ◽  
Author(s):  
Ron Galant ◽  
Christopher M. Walsh ◽  
Sean B. Carroll
Keyword(s):  
Binding Sites ◽  
Target Gene ◽  
Target Genes ◽  
Hox Genes ◽  
Regulatory Element ◽  
Morphological Diversity ◽  
Hox Proteins ◽  
Cis Element ◽  
Additive Action ◽  
Hox Protein

Homeotic (Hox) genes regulate the identity of structures along the anterior-posterior axis of most animals. The low DNA-binding specificities of Hox proteins have raised the question of how these transcription factors selectively regulate target gene expression. The discovery that the Extradenticle (Exd)/Pbx and Homothorax (Hth)/Meis proteins act as cofactors for several Hox proteins has advanced the view that interactions with cofactors are critical to the target selectivity of Hox proteins. It is not clear, however, to what extent Hox proteins also regulate target genes in the absence of cofactors. In Drosophila melanogaster, the Hox protein Ultrabithorax (Ubx) promotes haltere development and suppresses wing development by selectively repressing many genes of the wing-patterning hierarchy, and this activity requires neither Exd nor Hth function. Here, we show that Ubx directly regulates a flight appendage-specific cis-regulatory element of the spalt (sal) gene. We find that multiple monomer Ubx-binding sites are required to completely repress this cis-element in the haltere, and that individual Ubx-binding sites are sufficient to mediate its partial repression. These results suggest that Hox proteins can directly regulate target genes in the absence of the cofactor Extradenticle. We propose that the regulation of some Hox target genes evolves via the accumulation of multiple Hox monomer binding sites. Furthermore, because the development and morphological diversity of the distal parts of most arthropod and vertebrate appendages involve Hox, but not Exd/Pbx or Hth/Meis proteins, this mode of target gene regulation appears to be important for distal appendage development and the evolution of appendage diversity.

The lines gene of Drosophila is required for specific functions of the Abdominal-B HOX protein

Development ◽  
1998 ◽  
Vol 125 (7) ◽  
pp. 1269-1274 ◽  
Author(s):  
J. Castelli-Gair
Keyword(s):  
Hox Genes ◽  
Hox Proteins ◽  
Normal Functions ◽  
Transcriptional Cofactors ◽  
Segment Polarity ◽  
Direct Target ◽  
Hox Protein ◽  
Segment Polarity Gene ◽  
Anterior Posterior ◽  
Polarity Gene

The Hox genes encode homeobox transcription factors that control the formation of segment specific structures in the anterior-posterior axis. HOX proteins regulate the transcription of downstream targets acting both as repressors and as activators. Due to the similarity of their homeoboxes it is likely that much of the specificity of HOX proteins is determined by interaction with transcriptional cofactors, but few HOX cofactor proteins have yet been described. Here I present genetic evidence showing that lines, a segment polarity gene of Drosophila, is required for the function of the Abdominal-B protein. In lines mutant embryos Abdominal-B protein expression is normal but incapable of promoting its normal functions: formation of the posterior spiracles and specification of an eighth abdominal denticle belt. These defects arise because in lines mutant embryos the Abdominal-B protein cannot activate its direct target empty spiracles or other downstream genes while it can function as a repressor of Ultrabithorax and abdominal-A. The lines gene seems to be required exclusively for Abdominal-B but not for the function of other Hox genes.

scholarly journals Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao Jin ◽  
Lu Dai ◽  
Yilan Ma ◽  
Jiayan Wang ◽  
Haihao Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Meta Analysis ◽  
Tumour Size ◽  
Therapeutic Targets ◽  
Cochrane Library ◽  
Clinical Value ◽  
Hox Proteins ◽  
Aberrant Expression ◽  
Hox Protein

Abstract Background An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and action mechanisms of HOX proteins in GC. Methods A comprehensive search of PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX protein expression on the prognosis and clinicopathological features of GC, respectively. Results Nineteen studies containing 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I2 = 90.5%, p = 0.000). According to the subgroup analysis, increased expression of HOX protein in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36–0.59, I2 = 3.1%, p = 0.377), while overexpression of HOX protein in the upregulated subgroup was correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79–3.74, I2 = 73.5%, p = 0.000). The aberrant expression of HOX protein was crucially related to the TNM stage, depth of tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC. In addition, the molecular mechanisms by which HOX proteins regulate tumorigenesis and development of GC were also explored. Conclusions HOX proteins play vital roles in GC progression, which might serve as prognostic markers and therapeutic targets for GC.

scholarly journals Roles of the HOX Proteins in Cancer Invasion and Metastasis

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 10
Author(s):  
Ana Paço ◽  
Simone Aparecida de Bessa Garcia ◽  
Joana Leitão Castro ◽  
Ana Rita Costa-Pinto ◽  
Renata Freitas
Keyword(s):  
Molecular Mechanisms ◽  
Hox Genes ◽  
Noncoding Rnas ◽  
Molecular Networks ◽  
Regulatory Effect ◽  
Invasion And Metastasis ◽  
Hox Proteins ◽  
Premetastatic Niche ◽  
Genes Expression ◽  
Hox Clusters

Invasion and metastasis correspond to the foremost cause of cancer-related death, and the molecular networks behind these two processes are extremely complex and dependent on the intra- and extracellular conditions along with the prime of the premetastatic niche. Currently, several studies suggest an association between the levels of HOX genes expression and cancer cell invasion and metastasis, which favour the formation of novel tumour masses. The deregulation of HOX genes by HMGA2/TET1 signalling and the regulatory effect of noncoding RNAs generated by the HOX loci can also promote invasion and metastasis, interfering with the expression of HOX genes or other genes relevant to these processes. In this review, we present five molecular mechanisms of HOX deregulation by which the HOX clusters products may affect invasion and metastatic processes in solid tumours.

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