Sox6is a candidate gene forp100Hmyopathy, heart block, and sudden neonatal death

Hagiwara, Nobuko; Klewer, Scott E.; Samson, Ricardo A.; Erickson, Drew T.; Lyon, Mary F.; Brilliant, Murray H.

doi:10.1073/pnas.97.8.4180

Cited by 75 publications

(96 citation statements)

References 36 publications

(44 reference statements)

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“…This suggestion can explain the postnatal lethal phenotype of homozygote mutant mice where a chromosomal inversion affects the Sox6 gene (29) and of mice with a targeted mutation of both Sox6 alleles (30). The striking finding that SRY can complement splicing activity of a nuclear extract that has been depleted of SOX6 indicates a role in splicing also for the testis-determining factor.…”

Section: Discussionmentioning

confidence: 95%

A direct role of SRY and SOX proteins in pre-mRNA splicing

Ohe

Lalli

Sassone–Corsi

2002

Proc. Natl. Acad. Sci. U.S.A.

108

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The mammalian testis determining factor SRY and its related Sox factors are critical developmental regulators. They share significant similarity in their high mobility group (HMG) domain and display discrete patterns of tissue-specific expression. Here we show that SRY and the Sox protein SOX6 colocalize with splicing factors in the nucleus and are dynamically redistributed following the blockage of splicing in living cells. Anti-SOX6 antibodies supershift the spliceosomal complex from assembled splicing reactions and inhibit splicing in vitro of multiple pre-mRNA substrates. Most importantly, SOX6-depleted nuclear extracts have impaired splicing activity, which is efficiently restored by addition of the recombinant SOX6 HMG domain and also by recombinant SRY and the SOX9 HMG domain. These results reveal an unexpected biological function of the SRY, SOX6, and SOX9 gene products and provide a functional link to the biochemical mechanisms operating in mammalian sex determination and in other developmental processes regulated by Sox genes.T he high mobility group (HMG)-type DNA binding domain was originally described as a domain in the RNA polymerase I transcription factor hUBF homologous to two regions in the chromatin HMG protein 1 (1). Proteins containing HMG domains have been found in a large variety of species and are grouped into two families, based on evolutionary and functional conservation (reviewed in ref.2). One family comprises the chromosomal HMG domain group of proteins, which are provided with two or more HMG domains and bind DNA with low to moderate affinity and little sequence specificity. The other family includes sequence-specific transcription factors, which are provided with only one HMG domain and bind to DNA sequences in the promoter of target genes to elicit their transcriptional activation. HMG domain factors bind DNA in the minor groove, induce a relevant DNA bending on binding, and are capable of binding to special or distorted DNA structures, such as four-way junctions, cis-platinum adducts, and base bulges (reviewed in ref.3). Given these properties, HMG domain proteins are postulated to act as architectural elements, promoting formation of contacts between factors bound at distant sites on DNA or recruiting proteins that by themselves do not bind to DNA and facilitating the assembly of higher-order complexes involved in transcriptional control, gene recombination, and DNA repair.Among sequence-specific HMG-domain proteins, a distinct position is occupied by the Sox (SRY box) protein family. A common feature of these proteins is to share more than 50% similarity in their HMG domains to SRY, the testis-determining factor located on human and mouse Y chromosomes. Sox proteins have been identified in a number of vertebrates and invertebrates, including Drosophila melanogaster and Caenorhabditis elegans. Outside the HMG box, Sox proteins are poorly conserved, and many are expressed with a tissue-specific pattern. These factors play a crucial role in development, as also shown by their invol...

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Section: Discussionmentioning

confidence: 95%

A direct role of SRY and SOX proteins in pre-mRNA splicing

Ohe

Lalli

Sassone–Corsi

2002

Proc. Natl. Acad. Sci. U.S.A.

108

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“…Two major size classes of SOX6 transcripts in mouse (Hagiwara et al, 2000), rat (Narahara et al, 2002), and human (Cohen-Barak et al, 2001) have been demonstrated: a small transcript of about 3 kb and a large one of 8-9 kb. The size difference is thought to be owing to the different sizes of the 3 0 and 5 0 UTRs (Lefebvre et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…The SOX6 gene showed significantly higher expression in all the glioma tissues analysed than in the normal adult brain ( Figure 3b). The large and small transcripts of SOX6 have been reported in mouse (Lefebvre et al, 1998;Hagiwara et al, 2000) and human (Cohen-Barak et al, 2001), and the size difference is most likely owing to the different sizes of the 3 0 and 5 0 untranslated regions (UTRs) (Lefebvre et al, 1998). The small transcript is predominantly expressed in the adult mouse testis and the large one is expressed in the developing mouse brain and mouse chondrocytes, but the expression significantly decreases in these adult tissues (Connor et al, 1995;Lefebvre et al, 1998).…”

Section: Analysis Of Sox6 Gene Expression In Gliomamentioning

confidence: 99%

Identification of a human glioma antigen, SOX6, recognized by patients' sera

et al. 2003

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“…The short form mSox6 was expressed predominantly in neonatal brain and adult testis. 32) By contrast, the long form mSox6 was most abundantly expressed in skeletal muscle, although it was expressed at varied levels in the other tissues such as heart, spleen, liver, and kidney of adult mouse. 32) In this study, rSox6 expression could not be detected in the organs except neonatal brain, adult testis, whole eye and ovary.…”

Section: Fig 2 Nucleotide Sequence Of Rsox6 Cdna and Comparison Ofmentioning

confidence: 94%

“…24) Since these motifs of Sox6 were conserved in the rSox6, rSox6 was suggested to have the same function as that of the reported Sox6. 24,26,[32][33][34] Organ Distributions of the rSox6 Gene Mouse Sox6 was reported to be expressed in neonatal brain and adult testis.…”

Section: Fig 2 Nucleotide Sequence Of Rsox6 Cdna and Comparison Ofmentioning

confidence: 99%

cDNA Cloning of the Sry-Related Gene Sox6 from Rat with Tissue-Specific Expression.

Narahara

Yamada

Hamada-Kanazawa

et al. 2002

Biological & Pharmaceutical Bulletin

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Previously, we isolated a novel compound from the neonatal rat brain and identified it as b-citryl-L-glutamate (b-CG). [1][2][3] In addition, b-CG was found in not only the brain of neonatal rats but also the testis and lens of adult rats. 4,5) This compound appeared at high concentrations during the period characterized by growth and differentiation of neurons, spermatozoa and lens-fibercells in each tissue. [4][5][6][7] Recently, we found two facts. 1. b-CG was localized exclusively in the primary cultured neurons 6) and in the neurons which differentiated from retinoic acid-treated P19 cells.8) P19 is a cell line derived from mouse embrional carcinomas (EC). 9) 2. The concentration of b-CG increased significantly with the differentiation of P19 cells into neurons.8) b-CG may play important roles in the growth and differentiation in the brain, testis and lens. However, the functional roles of b-CG are unclear.While, SRY, a candidate gene responsible for testis determination, has been isolated from the sex determining regions of human and mouse Y chromosome.10,11) SRY encodes a protein with a DNA-binding motif known as the high-mobility-group (HMG) box. 10,11) In addition to SRY, genes encoding an SRY-type HMG box (SOX genes/sox) have been identified by polymerase chain reaction (PCR) with primers based on the conserved amino acid sequence of the HMG boxes of mammalian SRY. [12][13][14][15][16][17][18] No less than 30 types of SOX gene have been isolated from humans, 19) mice and rainbow trout, and they have been considered to be related to the regulation of cell differentiation and to the differentiation pattern. 17,[20][21][22][23] Sox6 showed the characteristic expression pattern and distribution among the sox family and it was specifically expressed during cell differentiation in tissues including the immature brain and adult testis. 24,25) The developmental changes in the brain or testis and tissues distributions of Sox6 were markedly similar to those of b-CG studied by us.2-4) Therefore, we have the interest for the relationship between Sox6 and b-CG.Sox6 has been cloned only in mice, 25) human 26) and rainbow trout, 24) and thought to function as a transcriptional regulation factor. Sox6 was preferentially expressed, when 3 kinds of cells including nerve cell, spermatide and the optic vesicle cell differentiated, and b-CG in these cells also remarkably increased in the same time. However the developmental changes and distributions of b-CG have been mainly examined in rats.2-4) So, we intended to examine the cloning of the Sox6 gene from rat and the distributions of rSox6 (rat Sox6) mRNA. In this study, rSox6 cDNA was cloned by PCR with primers based on the mSox6 (mouse Sox6) cDNA from the adult rat testis cDNA library. The organ distribution and the developmental changes were examined by Northern blotting and a Real-time quantitative reverse transcription (RT)-PCR method. MATERIALS AND METHOD MaterialsThe SuperScript cloning system and Escherichia coli DH5a competent cells were obtained from GIBCO/BRL an...

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Sox6is a candidate gene forp^100Hmyopathy, heart block, and sudden neonatal death

Cited by 75 publications

References 36 publications

A direct role of SRY and SOX proteins in pre-mRNA splicing

A direct role of SRY and SOX proteins in pre-mRNA splicing

Identification of a human glioma antigen, SOX6, recognized by patients' sera

cDNA Cloning of the Sry-Related Gene Sox6 from Rat with Tissue-Specific Expression.

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