From head to toes: the multiple facets of Sox proteins
Nucleic Acids ResearchPublished 15 March 1999Open access
Michael Wegner
Citations891
SJR quartileQ1
SJR score7.78
SNIP4.71
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TL;DR
Sox proteins perform their function in a complex interplay with other transcription factors in a manner highly dependent on cell type and promoter context, and exhibit a remarkable crosstalk and functional redundancy among each other.
Abstract
Sox proteins belong to the HMG box superfamily of DNA-binding proteins and are found throughout the animal kingdom. They are involved in the regulation of such diverse developmental processes as germ layer formation, organ development and cell type specifi-cation. Hence, deletion or mutation of Sox proteins often results in developmental defects and congenital disease in humans. Sox proteins perform their function in a complex interplay with other transcription factors in a manner highly dependent on cell type and promoter context. They exhibit a remarkable crosstalk and functional redundancy among each other.
Keywords
Social SciencesBiochemistry, Genetics and Molecular Biology
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802 Citations1998Véronique Lefèbvre, Ping Li +1 more
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660 Citations1995Edwina M. Wright, Murray Hargrave +7 more
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595 Citations1998Pascal de Santa Barbara, Nathalie Bonneaud +7 more
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572 Citations1995Adam Hacker, Blanche Capel +2 more
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DevelopmentA role for SOX1 in neural determination
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468 Citations1995Milton H. Werner, Jeffrey R. Huth +2 more
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It is shown here also that the HMG box of SRY, the protein that determines the expression of male‐specific genes in humans, recognizes four‐way junction DNAs irrespective of their sequence.
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A mutation in SRY is identified in one out of 12 sex-inversed XY females with gonadal dysgenesis who do not lack large segments of the short arm of the Y chromosome5-8, providing strong evidence for SRY being TDF.
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390 Citations1995Dafe Uwanogho, Maria Rex +5 more
Three chicken Sox (SRY-like box) genes have been identified that show an interactive pattern of expression in the developing embryonic nervous system, suggesting that Sox genes play a role in neural development and that the developmental programme from immature to mature neurons may involve switching of Sox gene expression.
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382 Citations1994Vincent R. Harley, Robin Lovell‐Badge +1 more
The HMG box family is functionally diverse, with members involved in DNA recognition during nucleosome assembly, recombination and transcription likely to be transcription factors and include the mammalian testis deteimnining factor (SRY), T-cell factor, lymphoid enhancer factor and the yeast sterility factor.
Molecular and Cellular BiologySynergistic Activation of the Fibroblast Growth Factor 4 Enhancer by Sox2 and Oct-3 Depends on Protein-Protein Interactions Facilitated by a Specific Spatial Arrangement of Factor Binding Sites
368 Citations1997Davide-Carlo Ambrosetti, Claudio Basilico +1 more
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Proceedings of the National Academy of SciencesMutation of the Sry-related <i>Sox10</i> gene in <i>Dominant megacolon</i> , a mouse model for human Hirschsprung disease
358 Citations1998Beate Herbarth, Véronique Pingault +7 more
The transcriptional regulator Sox10 is identified as an essential factor in mouse neural crest development and as a further candidate gene for human Hirschsprung disease, especially in cases where it is associated with features of Waardenburg syndrome.
CellXsox17α and -β Mediate Endoderm Formation in Xenopus
351 Citations1997C. S. Hudson, Debbie Clements +3 more
The isolation of two Xenopus relatives of murine Sox17 expressed in gastrula presumptive endoderm and the effects of the mRNAs on embryo phenotypes suggest that the Xsox17 genes mediate an activin-induced endODerm differentiation pathway in animal caps and are involved in normal endoderman differentiation in embryos.
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344 Citations1993Marc van de Wetering, Mariëtte A. Oosterwegel +2 more
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DevelopmentInvolvement of <i>Sox1, 2</i> and <i>3</i> in the early and subsequent molecular events of lens induction
336 Citations1998Yusuke Kamachi, Masanori Uchikawa +3 more
An essential molecular event in lens induction is the 'turning on' of the transcriptional regulators SOX2/3 in the Pax6-expressing ectoderm and these SOX proteins activate crystallin gene expression.
Nucleic Acids ResearchAncestry and diversity of the HMG box superfamily
329 Citations1993Vincent Laudet, D. Stéhelin +1 more
By studying the extent of diversification of the HMG box superfamily, it is found that the speed of evolution was very different within the various groups of HMG-box containing factors.
Genes & DevelopmentNew POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2
319 Citations1998V. Botquin, Heike Hess +5 more
DevelopmentXY female mice resulting from a heritable mutation in the primary testis determining gene, <i>Tdy</i>
317 Citations1990Robin Lovell‐Badge, Elizabeth J. Robertson
From the phenotype and deduced location of the mutation, it is concluded that it is within the Tdy locus, the first such mutation to be described in mice.
Genes & DevelopmentSox1 directly regulates the gamma -crystallin genes and is essential for lens development in mice
297 Citations1998Seiji Nishiguchi, Heather Wood +3 more
It appears that the direct interaction of the SOX1 protein with a promoter element conserved in all gamma-crystallin genes is responsible for their expression.
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290 Citations1994Andrea Pontiggia, Rebecca Rimini +4 more
The biochemical properties of the DNA binding domains (HMG‐boxes) of mutant SRY proteins from five patients with complete gonadal dysgenesis suggest that the exact spatial arrangement of the nucleoprotein complex organized by SRY is essential for sex determination.
Trends in GeneticsTCF/LEF factors earn their wings
288 Citations1997Hans Clevers, Marc van de Wetering
Proceedings of the National Academy of SciencesAn SRY-related sequence on the marsupial X chromosome:implications for the evolution of the mammalian testis-determininggene.
283 Citations1994Jamie W. Foster, Jennifer A. Marshall Graves
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The EMBO JournalAn SRY‐related gene expressed during spermatogenesis in the mouse encodes a sequence‐specific DNA‐binding protein.
258 Citations1992Paul Denny, S Swift +2 more
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257 Citations1993Milena Stevanovlć, Robin Lovell‐Badge +2 more
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256 Citations1993Michael Wegner, Daniel W. Drolet +1 more
Analysis of the means by which POU-domain proteins regulate transcription has led to a further understanding of how this group initiates specific developmental programs.
The EMBO JournalInvolvement of SOX proteins in lens‐specific activation of crystallin genes.
236 Citations1995Yusuke Kamachi, Shanthini Sockanathan +4 more
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Developmental DynamicsDynamic expression of chicken Sox2 and Sox3 genes in ectoderm induced to form neural tissue
229 Citations1997Maria Rex, Alex Orme +5 more
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225 Citations1998Kirsten Kuhlbrodt, Beate Herbarth +4 more
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212 Citations1993Edwina M. Wright, Bernadette Snopek +1 more
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Science<i>Mixer</i> , a Homeobox Gene Required for Endoderm Development
205 Citations1998Gilbert L. Henry, Douglas A. Melton
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202 Citations1997Jobst Meyer
Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance and instability of the mutant SOX9 protein as demonstrated by Western blotting.
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188 Citations1998Emmanuelle Oréal, Claude Pieau +5 more
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149 Citations1992Paul Denny, Sally Swift +4 more
Sequencing of the cloned PCR products demonstrated that they were heterogeneous, with the clones falling into a few, distinct classes, mostly differing from those SRY-related clones previously described, and the strong evolutionary conservation of this gene family suggests that the SRy-related genes may be of importance in developmental processes.
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147 Citations1994Frances Connor, Peter D. Cary +6 more
Analysis of the structure of the Sox-5 HMG box by 2D NMR suggests that both the location of helical secondary structure as well as the tertiary structure is similar to that of HMG1 box 2.
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145 Citations1995Frances Connor, Edwina M. Wright +3 more
Cloned and sequenced a full-length cDNA for the HMG box-containing, SRY-related gene Sox6 from mouse, which suggests that the two genes may have overlapping functions in the regulation of gene expression during spermatogenesis in the adult mouse.
DevelopmentThe <i>Dichaete</i> gene of <i>Drosophila melanogaster</i> encodes a SOX-domain protein required for embryonic segmentation
144 Citations1996Steven Russell, Natalia Sánchez‐Soriano +2 more
A member of the High Mobility Group superfamily of genes from Drosophila, Sox70D, is cloned and characterised, which is closely related to the mammalian testis determining gene SRY and corresponds to the dominant wing mutation Dichaete, suggesting that the gene plays a key role in early development.
NeuronSoxD
140 Citations1998Kenji Mizuseki, Masashi Kishi +3 more
Data show that SoxD functions as an essential mediator of downstream signaling of neural induction and can block neuralization of ectoderm caused by attenuation of BMP signals and can strongly suppress formation of anterior neural tissues in vivo.
Journal of Biological ChemistryFunctional Analysis of Sox10 Mutations Found in Human Waardenburg-Hirschsprung Patients
139 Citations1998Kirsten Kuhlbrodt, Claudia Schmidt +5 more
Analysis of the naturally occurring Sox10 mutations not only helps to dissect Sox10 structure, but also allows limited predictions on the severity of the disease.
Current Opinion in Cell BiologyTCF: transcriptional activator or repressor?
137 Citations1998Mariann Bienz
T cell factor, or TCF, has been identified as the transcriptional response factor activated by Wnt-1 and Wingless signalling, thought to be a potent architectural factor which facilitates assembly of multiprotein enhancer complexes.
Human GeneticsThe SOX10 / Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor
134 Citations1998Carsten M. Pusch, Elisabeth Hustert +8 more
Cloned and sequenced the SOX10 and Sox10 genes from human and mouse, respectively, finding that a Sox10 mutation underlies the mouse mutant Dom, a murine Hirschsprung model, and is likely to function as a transcription factor.
Developmental DynamicsExpression of theSox11 gene in mouse embryos suggests roles in neuronal maturation and epithelio-mesenchymal induction
133 Citations1997Murray Hargrave, Edwina M. Wright +4 more
expression of Sox11 in mouse embryos was prominent in the periventricular cells of the central nervous system, suggesting a role in neuronal maturation and a wide range of tissues involved in epithelial‐mesenchymal interactions, suggesting an additional role in tissue modelling during development.
CellArchitectural Transcription Factors: Proteins That-Remodel DNA
130 Citations1997Milton H. Werner, S.K. Burley
The immediate challenge facing molecular biologists is to go beyond mere physical descriptions of these systems and characterize the kinetic and thermodynamic consequences of building transcriptionally active stereo-specific nucleoprotein complexes.
Molecular EndocrinologySry is a transcriptional activator.
121 Citations1994Robert Dubin, Harry Ostrer
These studies suggest that both the human and the mouse SRY ORFs encode nuclear, DNA- binding proteins and that the mouse Sry ORF can function as a transcriptional activator with separable DNA-binding and activator domains.
The Journal of Cell BiologyNuclear localization of the testis determining gene product SRY.
118 Citations1995Françis Poulat, F Girard +6 more
It is demonstrated that the localization of the p27SRY protein into the nucleus was an event involving the NH2-terminal part of the high mobility group (HMG) domain, suggesting common properties of nuclear targeting within the HMG box protein family.
DevelopmentThe <i>Drosophila fish-hook</i> gene encodes a HMG domain protein essential for segmentation and CNS development
116 Citations1996Patricia A. Nambu, John R. Nambu
Results indicate an essential role for fish in anterior/posterior pattern formation and nervous system development, and suggest a potential function in modulating the activities of gap and pair-rule proteins.
FEBS LettersExpression of the <i>SOX10</i> gene during human development
115 Citations1998Nadège Bondurand, Alexandra Kobetz +8 more
The spatial and temporal pattern of SOX10 expression supports an important function in neural crest development in humans, and was more widely expressed in humans than in rodents.
European Journal of ImmunologySox‐4 facilitates thymocyte differentiation
108 Citations1997Marco W. Schilham, Petra Moerer +2 more
It is concluded that Sox‐4 facilitates thymocyte development, and this effect was T cell‐autonomous, since similar observations were made when FTOC were performed by culturing of Sox‐ 4‐deficient progenitors in wild‐type thymus lobes.
DevelopmentThe Drosophila SOX-domain protein Dichaete is required for the development of the central nervous system midline
105 Citations1998Núria Soriano, Steven Russell
The data suggest that the SOX gene structure, function and interactions have been conserved during evolution, and that Dichaete mutations are rescued by expression of mouse SOX2.
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103 Citations1996Heather Prior, Michael A. Walter
The SOX gene family, named for a shared motif called the SRY box a region homologous to the DNA-binding domain of SRY, the mammalian sex determining gene, plays important roles in chordate development.
Human GeneticsTranslocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9
97 Citations1996Jutta Wirth, Thomas Wagner +5 more
By using a SOX9 coding sequence polymorphism, expression of bothSOX9 alleles has been demonstrated by the reverse transcriptase polymerase chain reaction in lymphoblastoid cells from one of the translocation cases.
Human MutationMutational analysis ofSRY in XY females
87 Citations1993J. Ross Hawkins
A total of 11 mutations in SRY have now been described, all in the DNA‐binding HMG‐box region of the gene, and all in patients with apparently complete gonadal dysgenesis, and surprisingly, three familial SRY mutations have been identified.
GenomicsThe Human SOX11 Gene: Cloning, Chromosomal Assignment and Tissue Expression
84 Citations1995Philippe Jay, Catherine Gozé +5 more
The human SOX11 gene is cloned and characterized using the partial cloning of both human and mouse SoX11 genes and mapped it to chromosome 1p25.
Journal of Biological ChemistryPhosphorylation of an N-terminal Motif Enhances DNA-binding Activity of the Human SRY Protein
83 Citations1998Marion Desclozeaux, Françis Poulat +8 more
The results strongly support the hypothesis that human SRY is a natural substrate for PKA in vivo and that this phosphorylation significantly modulates its major activity, DNA-binding, thereby possibly altering its biological function.
GenomicsCloning and Characterization ofSOX5,a New Member of the HumanSOXGene Family
81 Citations1996Véronique M. Wunderle, Ricky Critcher +2 more
Cloned SOX5, a new member of the human SOX gene family, shows a high similarity with the mouse Sox5 transcript over a large region identical in all the human cDNAs, however, comparison of the 5' unique sequences of the c DNAs suggests that the SOx5 gene is subject to alternative splicing.
BiochemistryHuman Testis-Determining Factor SRY Binds to the Major DNA Adduct of Cisplatin and a Putative Target Sequence with Comparable Affinities
78 Citations1998Elizabeth E. Trimmer, Deborah B. Zamble +2 more
The data suggest that cisplatin-DNA adducts may compete with specific DNA sequences in vivo for the binding of human SRY, and a possible role for this testis-specific protein in the cytotoxicity and organotropic specificity of cisPlatin for testicular tumors is proposed.
Journal of Biological ChemistrySolution Structure of the Sequence-specific HMG Box of the Lymphocyte Transcriptional Activator Sox-4
75 Citations1995Leo P. A. Van Houte, V. P. Chuprina +4 more
The solution structure of the sequence-specific HMG-box of the SRY-related protein Sox-4 is reported, which is L-shaped and is maintained by a cluster of conserved, mainly aromatic residues.
GeneRainbow trout SOX9: cDNA cloning, gene structure and expression
71 Citations1997Nobuhiko Takamatsu, Hiromi Kanda +4 more
The rainbow trout and human SOX9 genes show a similar gene structure, and the two introns in the coding region are located at conserved positions.
Molecular and Cellular BiologyA Gene That Is Related to <i>SRY</i> and Is Expressed in the Testes Encodes a Leucine Zipper-Containing Protein
69 Citations1995Nobuhiko Takamatsu, Hiromi Kanda +6 more
SRY-related cDNA encoding a protein with a high-mobility-group (HMG) box and a leucine zipper motif, which was designated SOX-LZ, was isolated from a rainbow trout testis cDNA library and exhibits an overall amino acid sequence identity of 77%, which is in striking contrast to the abrupt loss of amino acids sequence homology outside the HMG box found among mammalian SRY genes.
GeneSequence and expression of Sox-18 encoding a new HMG-box transcription factor
55 Citations1995Timothy L. Dunn, Lesley Mynett‐Johnson +4 more
The full cDNA sequence of Sox-18 which encodes a protein of 378 aa is determined and it is reported here the identification of two new members of this family, Sox-17 and 18.
Mechanisms of DevelopmentGene regulatory functions of Drosophila Fish-hook, a high mobility group domain Sox protein
53 Citations1998Yue Ma, Emily Niemitz +6 more
It is determined that Fish protein is expressed in a dynamic pattern throughout embryogenesis, and is present in nuclear and cytoplasmic compartments.
Mechanisms of DevelopmentcSox21 exhibits a complex and dynamic pattern of transcription during embryonic development of the chick central nervous system
51 Citations1997Maria Rex, Dafe Uwanogho +3 more
The expression of cSox21, and other genes (such as Delta, Serrate and Pax genes), may play a part in defining the developmental fate of cells along the dorsoventral axis.
Human Molecular GeneticsSOX22 is a new member of the SOX gene family, mainly expressed in human nervous tissue
49 Citations1997Philippe Jay
The cloning of a new human member of the SOX gene family, SOX22, is reported, suggesting that this gene plays roles in both differentiation and maintenance of several cell types.
Nucleic Acids ResearchHigh expression of the HMG box factor Sox-13 in arterial walls during embryonic development
45 Citations1998Jeroen P. Roose, Wouter Korver +6 more
The cloning and initial analysis of murine Sox-13 is reported, which reveals a single HMG box, a leucine zipper motif and a glutamine-rich stretch that likely plays an important role in development.
GeneThe zebrafish Zf-Sox 19 protein: a novel member of the Sox family which reveals highly conserved motifs outside of the DNA-binding domain
42 Citations1995Sophie Vriz, Robin Lovell‐Badge
There are blocks of amino acids showing considerable identity with regions of Sox-1, -2 and -3 that may represent conserved parts of the protein, required for interaction with other proteins, and strengthen the assignment of the zebrafish gene, termed Zf-sox 19, to the B subfamily.
BiochemistryAn SRY Mutation Causing Human Sex Reversal Resolves a General Mechanism of Structure-Specific DNA Recognition: Application to the Four-Way DNA Junction
40 Citations1995Richard Peters, Chih‐Yen King +4 more
Clinical association of the I68T mutation with human sex reversal supports the hypothesis that specific DNA recognition by SRY is required for male sex determination and rationalizes patterns of sequence conservation or diversity among HMG boxes.
GenomicsIsolation of a NovelSry-Related Gene That Is Expressed in High-Metastatic K-1735 Murine Melanoma Cells
37 Citations1997Masachika Tani, Nobuko Shindo‐Okada +5 more
Results suggest that expression of the Sox21 gene is involved in the development of nerve systems and may function to enhance the metastatic potential of K-1735 mouse melanoma cells of nerve cell origin.
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