An ancient family of embryonically expressed mouse genes sharing a conserved protein motif with the T locus

Bollag, Roni J.; Siegfried, Zahava; Cebra‐Thomas, Judith A.; Garvey, Nancy; Davison, Ewa M.; Silver, Lee M.

doi:10.1038/ng0794-383

Cited by 204 publications

(155 citation statements)

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“…4,5 TBX3 belongs to the T-box gene family, which encodes a large family of transcription factors sharing a DNA-binding domain called the T-box. 4,6,7 Missense mutations, and nonsense mutations that result in impaired DNA binding as well as splice site mutations have been detected in UMS patients. 4,8 Single-base deletion and insertions (frameshift mutations) lead to a truncated protein lacking the T-box domain, which is incapable of binding DNA.…”

Section: Introductionmentioning

confidence: 99%

Ulnar–mammary syndrome with dysmorphic facies and mental retardation caused by a novel 1.28 Mb deletion encompassing the TBX3 gene

et al. 2006

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Ulnar -mammary syndrome (UMS) is a rare autosomal-dominant disorder caused by mutations in TBX3. The condition is characterized by hypoplasia or aplasia of upper limbs on the ulnar side, mammary glands and nipples, and of apocrine glands in both sexes (MIM #181450). We report on a girl presenting with an UMS like phenotype, a dysmorphic facies, and mental retardation. Mutation analysis of TBX3 and G-banded chromosome analysis from lymphocytes were performed. We used microarray-based comparative genomic hybridization (array CGH) to investigate the patient's genomic DNA for submicroscopic aberrations. No mutation of the TBX3 gene was detected in our patient and chromosome analysis revealed a normal female karyotype (46,XX). Hybridization of a whole-genome tiling path array consisting of more than 36 000 BAC clones revealed an interstitial 1.28 Mb deletion within chromosomal band 12q24.21. The deleted region encompasses one known gene, TBX3. The deletion and haploinsufficiency of TBX3 was confirmed by fluorescence in situ hybridization using BAC clones representing the deletion on the BAC array. To our knowledge, this is the first description of TBX3 haploinsufficiency caused by a genomic deletion in a patient with UMS. We suggest that the UMS phenotype in conjunction with the characteristic facial changes and mental retardation observed in our patient is owing to the deletion of TBX3 and the involvement of neighbouring genes.

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Section: Introductionmentioning

confidence: 99%

Ulnar–mammary syndrome with dysmorphic facies and mental retardation caused by a novel 1.28 Mb deletion encompassing the TBX3 gene

et al. 2006

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“…Over the past few years considerable excitement has been generated by the discovery, by Bollag et al, (9) of a novel family of transcription factors defined by the conservation of the T box, which corresponds approximately to the DNA binding domain (10,11). The T-box family plays a critical role in embryonic development (for reviews see Refs.…”

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confidence: 99%

The Gene Encoding the T-box Factor Tbx2 Is a Target for the Microphthalmia-associated Transcription Factor in Melanocytes

Carreira¹,

Liu²,

Goding

2000

Journal of Biological Chemistry

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Commitment to the melanocyte lineage is characterized by the onset of microphthalmia-associated transcription factor (Mitf) expression. Mitf plays a fundamental role in melanocyte development, with mice lacking Mitf being entirely devoid of pigment cells. In the absence of functional Mitf protein, melanoblasts expressing Mitf mRNA disappear around 2 days after their first appearance either by apoptosis or by losing their identity and adopting an alternative cell fate. The role of Mitf must therefore be to regulate genes required for melanoblast survival, proliferation, or the maintenance of melanoblast identity. Yet to date, Mitf has been shown to regulate genes such as Tyrosinase, Tyrp-1, and Dct, which are required for pigmentation, a differentiationspecific process. Because expression of these genes cannot account for the complete absence of pigment cells in Mitf-negative mice, Mitf must regulate the expression of other as yet uncharacterized genes. Here we provide several lines of evidence to suggest that Mitf may regulate the expression of the Tbx2 transcription factor, a member of the T-box family of proteins implicated in the maintenance of cell identity. First, isolation and sequencing of the entire murine Tbx2 gene revealed that the Tbx2 promoter contains a full consensus Mitf recognition element; second, Mitf could bind the promoter in vitro and activate Tbx2 expression in vivo in an E boxdependent fashion; and third, Tbx2 is expressed in melanoma cell lines expressing Mitf, but not in a line in which Mitf expression was not detectable. Taken together, with the fact that Tbx2 is expressed in Mitfpositive melanoblasts and melanocytes, but not in Mitfnegative melanoblast precursor cells, the evidence suggests that the Tbx2 gene may represent one of the first known targets for Mitf that is not a gene involved directly in the manufacture of pigment.Understanding how specific cell lineages are established and maintained lies at the heart of developmental biology. The melanocyte lineage arises in the neural crest as nonpigmented precursor cells, termed melanoblasts, which then migrate to their final destinations in the epidermis and hair follicles, where they differentiate into mature pigment-producing melanocytes. Little is known of the precise program of events leading from a multipotent neural crest cell to a melanoblast, but the switch from a melanoblast precursor cell to a melanoblast is characterized by the onset of expression of the basic-helixloop-helix-leucine zipper (bHLH-LZ)

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“…We have s h o w n that the h u m a n T gene is (Bollag et al 1994), a n d h u m a n TBX2 has b e e n m a p p e d to 17q23 (Agulnik et al 1995). However the finding that four T-box genes of C. elegans are closely linked in c h r o m o s o m e III (Agulnik et al 1995) suggests that clusters of T-box genes m a y exist in vertebrate species but have n o t yet b e e n identified.…”

Section: Discussionmentioning

confidence: 99%

“…The tunicate homolog As-T and Drosophila Trg (Kispert et al 1994) both show a lower level of identity (46%). In every case the highest level of conservation is found in the DNAbinding domain (Bollag et al 1994); 80%-98% when human T is compared to vertebrate sequence and 64% is compared to Dro3phila Trg. In contrast with the high level of sequence identity between human T and T from other vertebrates, there appears to be relatively less similarity between T and other T-box protein se-…”

Section: Genome Research @ 227mentioning

confidence: 99%

“…A protein motif within the DNA-binding domain, the so-called T-box, is highly conserved among T homologs from different species and also defines a broader family of T-box genes. These include a human gene TBX2 (Campbell et al 1995), the mouse genes Tbxl, Tbx2, and Tbx3 (Bollag et al 1994), the Drosophila genes Trg (Kispert et al 1994) and optomotor blind (omb) (Pflugfelder et al 1992), the sea urchin gene HpTa (Harada et al 1995) and four Caenorhabditis elegans genes (Agulnik et al 1995).…”

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confidence: 99%

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The human homolog T of the mouse T(Brachyury) gene; gene structure, cDNA sequence, and assignment to chromosome 6q27.

Edwards¹,

Putt²,

Lekoape³

et al. 1996

Genome Res.

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We have cloned the human gene encoding the transcription factor T. T protein is vital for the formation of posterior mesoderm and axial development in all vertebrates. Brachyury mutant mice, which lack T protein, die in utero with abnormal notochord, posterior somites, and allantois. We have identified human T genomic clones and derived the mRNA sequence and gene structure. There is 91% amino acid identity between human and mouse T proteins overall and complete identity across 77 amino acids of the T-box motif within the DNA-binding domain. Human T expression is very similar to that found for T in other vertebrate species and is confined to cells derived from the notochord. The human T gene maps to chromosome 6q27 and is only the second human member of the T-box gene family to be described.

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An ancient family of embryonically expressed mouse genes sharing a conserved protein motif with the T locus

Cited by 204 publications

References 20 publications

Ulnar–mammary syndrome with dysmorphic facies and mental retardation caused by a novel 1.28 Mb deletion encompassing the TBX3 gene

Ulnar–mammary syndrome with dysmorphic facies and mental retardation caused by a novel 1.28 Mb deletion encompassing the TBX3 gene

The Gene Encoding the T-box Factor Tbx2 Is a Target for the Microphthalmia-associated Transcription Factor in Melanocytes

The human homolog T of the mouse T(Brachyury) gene; gene structure, cDNA sequence, and assignment to chromosome 6q27.

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