Hox transcription factors and their elusive mammalian gene targets

Svingen, Terje; Tonissen, Kathryn Fay

doi:10.1038/sj.hdy.6800847

Cited by 141 publications

(136 citation statements)

References 72 publications

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“…They are considered as master regulators involved in fundamental processes during the development of an organism (Svingen and Tonissen, 2006). In recent years, abnormal expression of these genes has been linked with the emergence of various, solid and hematopoietic malignancies (16)(17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Alvarado-Ruíz¹,

Martínez-Silva²,

Torres-Reyes³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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HOX transcription factors are evolutionarily conserved in many different species and are involved in important cellular processes such as morphogenesis, differentiation, and proliferation. They have also recently been implicated in carcinogenesis, but their precise role in cancer, especially in cervical cancer (CC), remains unclear. In this work, using microarray assays followed by the quantitative polymerase chain reaction (qPCR), we found that the expression of 25 HOX genes was downregulated in CC derived cell lines compared with nontumorigenic keratinocytes. In particular, the expression of HOXA9 was observed as down-modulated in CCderived cell lines. The expression of HOXA9 has not been previously reported in CC, or in normal keratinocytes of the cervix. We found that normal CC from women without cervical lesions express HOXA9; in contrast, CC cell lines and samples of biopsies from women with CC showed significantly diminished HOXA9 expression. Furthermore, we found that methylation at the first exon of HOXA9 could play an important role in modulating the expression of this gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell proliferation and migration, and induced an epithelial-like phenotype. Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears to be a necessary step during CC development. Further studies are needed to delineate the role of HOXA9 during malignant progression and to afford more insights into the relationship between downmodulation of HOXA9 and viral HPV oncoprotein expression during cercical cancer development.

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Section: Discussionmentioning

confidence: 99%

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Alvarado-Ruíz¹,

Martínez-Silva²,

Torres-Reyes³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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“…As discussed above, the complexity and specificity of the interaction between proteins and DNA is not totally explained by the protein Svingen and Tonissen (2006) DNA-TBP Transcriptiondomains, because the DNA structure also influences these contacts, as it is dependent of several environment factors.…”

Section: Protein Domainsmentioning

confidence: 99%

“…A particular study related with the Hox family of transcription factors revealed that a core DNA consensus sequence is recognized by the majority of homeodomain proteins, raising the question as to how transcriptional and biological specificity can be obtained (Svingen and Tonissen, 2006). Although, sequence-specific binding is a critical part of transcriptional regulation and thus biological specificity, DNA sequence recognition alone is not the only determinant factor.…”

Section: Dna-transcription Factors Interactionmentioning

confidence: 99%

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Amino acids–nucleotides biomolecular recognition: from biological occurrence to affinity chromatography

Sousa

Cruz

Queiroz

2010

J of Molecular Recognition

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aIn this review, the protein-DNA interactions are discussed considering different perspectives, and the biological occurrence of this interaction is explained at atomic level. The evaluation of the amino acid-nucleotide recognition has been investigated analysing datasets for predicting the association preferences and the geometry that favours the interaction.Based on this knowledge, an affinity chromatographic method was developed also exploiting this biological favoured contact. In fact, the implementation of this technique brings the possibility to apply the concept of molecular interactions to the development of new purification methodologies. In addition, the integration of the information recovered by all the different perspectives can bring new insights about some biological mechanisms, though not totally clarified.

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“…The moving velocity of the LALI zone is determined by the ratio of the sizes of LALI zone at different stages, and it is approximated by We justify the change of parameters at the different phases of the simulation on the basis of the key role played by the dramatic changes in the distributions of Hox gene products in the apical zone at the different phases of limb development [14]. The Hox proteins are transcription factors that regulate the levels of developmentally important signals such as the activating and inhibitory morphogens of our model [21]. Although "recombinant" limb buds with disrupted Hox protein gradients can form limb skeletons with discrete jointed elements, the skeletons are grossly abnormal [30,18].…”

Section: Algorithm Convergence Analysis For a System With The Exact Smentioning

confidence: 99%

A Finite Element Model Based on Discontinuous Galerkin Methods on Moving Grids for Vertebrate Limb Pattern Formation

Zhu

Zhang

Newman

et al. 2009

Math. Model. Nat. Phenom.

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Abstract. Skeletal patterning in the vertebrate limb, i.e., the spatiotemporal regulation of cartilage differentiation (chondrogenesis) during embryogenesis and regeneration, is one of the best studied examples of a multicellular developmental process. Recently [Alber et al., The morphostatic limit for a model of skeletal pattern formation in the vertebrate limb, Bulletin of Mathematical Biology, 2008, v70, pp. 460-483], a simplified two-equation reaction-diffusion system was developed to describe the interaction of two of the key morphogens: the activator and an activator-dependent inhibitor of precartilage condensation formation. A discontinuous Galerkin (DG) finite element method was applied to solve this nonlinear system on complex domains to study the effects of domain geometry on the pattern generated [Zhu et al., Application of Discontinuous Galerkin Methods for reaction-diffusion systems in developmental biology, Journal of Scientific Computing, 2009, v40, pp. 391-418]. In this paper, we extend these previous results and develop a DG finite element model in a moving and deforming domain for skeletal pattern formation in the vertebrate limb. Simulations reflect the actual dynamics of limb development and indicate the important role played by the geometry of the undifferentiated apical zone.

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Hox transcription factors and their elusive mammalian gene targets

Cited by 141 publications

References 72 publications

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Amino acids–nucleotides biomolecular recognition: from biological occurrence to affinity chromatography

A Finite Element Model Based on Discontinuous Galerkin Methods on Moving Grids for Vertebrate Limb Pattern Formation

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