Transcription factor Sp3 is essential for post-natal survival and late tooth development

Bouwman, Peter; Göllner, Heike; Elsässer, Hans–Peter; Eckhoff, G.; Karis, Alar; Grosveld, Frank; Philipsen, Sjaak; Suske, Guntram

doi:10.1093/emboj/19.4.655

Cited by 172 publications

(173 citation statements)

References 33 publications

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“…Here we report that they are also involved in murine Nanog gene transcriptional regulation. However, Sp1 or Sp3 knockout mice were still able to form intact inner cell mass [13,14], suggesting that Sp1 and Sp3 have redundant functions that compensate for each other in Sp1 or Sp3 knockout mice, Perhaps the generation of ES cells with double knockout of Sp1 and Sp3 will unravel the question. …”

Section: Resultsmentioning

confidence: 99%

Functional analysis of two Sp1/Sp3 binding sites in murine Nanog gene promoter

Yao

2006

Cell Res

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Section: Resultsmentioning

confidence: 99%

Functional analysis of two Sp1/Sp3 binding sites in murine Nanog gene promoter

Yao

2006

Cell Res

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“…In contrast, Sp3-null mice develop normally with a reduction of body weight and die perinatally, probably because of respiratory failure. In Sp3-null tooth, ameloblasts fail to produce ameloblastin and amelogenin, and no enamel matrix layer is formed (15). Dental epithelium apparently proliferates, but secretory stage ameloblasts are de- fective.…”

Section: Discussionmentioning

confidence: 99%

“…Some Sp/KLF family proteins have been shown to play essential roles in tooth and skin formation. For example, Sp3 knockout mice revealed growth retardation and defective tooth enamel formation caused by the lack of the enamel matrix proteins amelogenin and ameloblastin (15). KLF4 knockout mice die perinatally because of loss of the barrier function of the skin (16).…”

mentioning

confidence: 99%

The Krüppel-like Factor Epiprofin Is Expressed by Epithelium of Developing Teeth, Hair Follicles, and Limb Buds and Promotes Cell Proliferation

Nakamura

Unda

de-Vega

et al. 2004

Journal of Biological Chemistry

112

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We identified a cDNA clone for epiprofin, which is preferentially expressed in teeth, by differential hybridization using DNA microarrays from an embryonic day 19.5 mouse molar cDNA library. Sequence analysis revealed that this cDNA encodes a member of the Krü ppellike factor family containing three characteristic C 2 H 2 -type zinc finger motifs. The full-length cDNA was obtained by the 5 Cap capture method. Except for its 5 -terminal sequence, the epiprofin mRNA sequence is almost identical to the predicted sequence of Krü ppellike factor 14/Sp6 (specificity protein 6), which was previously identified in expressed sequence tag data bases and GenBank TM by an Sp1 zinc finger DNA-binding domain search (Scohy, S., Gabant, P., Van Reeth, T., Hertveldt, V., Dreze, P. L., Van Vooren, P., Riviere, M., Szpirer, J., and Szpirer, C. (2000) Genomics 70, 93-101). This sequence difference is due to differences in the assignment of the location of exon 1. In situ hybridization revealed that epiprofin mRNA is expressed by proliferating dental epithelium, differentiated odontoblast, and also hair follicle matrix epithelium. In addition, whole mount in situ hybridization showed transient expression of epiprofin mRNA in cells of the apical ectodermal ridge in developing limbs and the posterior neuropore. Transfection of an epiprofin expression vector revealed that this molecule is localized in the nucleus and promotes cell proliferation. Thus, epiprofin is a highly cell-and tissue-specific nuclear protein expressed primarily by proliferating epithelial cells of teeth, hair follicles, and limbs that may function in the development of these tissues by regulating cell growth.

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“…Each AUG mutation resulted in the lack of the appropriate isoform in an in vitro transcription/ translation system (Fig. 2B, lanes [3][4][5][6]. Thus the four different isoforms derive from translational initiation at the four AUG sites leading to translation products of 781, 769, 496, and 479 amino acids that differ in their N-terminal end (Fig.…”

Section: All Four Sp3 Isoforms Are Derived From Alternative Translatimentioning

confidence: 98%

“…Sp3-deficient embryos develop until birth, but die invariably of respiratory failure immediately after birth (4). In addition, late tooth and bone developmental processes are impaired in Sp3Ϫ/Ϫ mice (4,5).…”

mentioning

confidence: 99%

Complexity of Translationally Controlled Transcription Factor Sp3 Isoform Expression

Sapetschnig¹,

Koch²,

Rischitor

et al. 2004

Journal of Biological Chemistry

Self Cite

100

105

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Sp3 is a ubiquitous transcription factor closely related to Sp1. Both proteins contain a highly conserved DNA-binding domain close to the C terminus and two glutamine-rich domains in the N-terminal moiety. Immunoblot analyses of Sp3 reveal a striking complex protein pattern of up to eight distinct species. This pattern is not observed in Sp3-deficient cell lines showing that all signals reflect Sp3 antigen. In this study, we have unraveled the complexity of Sp3 expression. We show that four isoforms of Sp3 that retain different parts of the N terminus are expressed in vivo. The four isoforms derive from alternative translational start sites at positions 1, 37, 856, and 907. An upstream open reading frame located at position ؊47 to ؊18 regulates expression of the two long isoforms. Unlike Sp1, none of the Sp3 isoforms is glycosylated. However, all four isoforms become SUMO-modified in vivo and in vitro specifically and exclusively at lysine residue 551. The transcriptional activity of the two long isoforms strongly depends on the promoter settings, whereas the small isoforms appear to be inactive. The transcriptional activity of all the Sp3 isoforms is regulated by SUMO modification. Our results demonstrate that Sp3 has many unique features and is not simply a functional equivalent of Sp1.The transcription factor Sp3 is a ubiquitously expressed member of the Sp family of transcription factor that is involved in the expression and regulation of many genes, including housekeeping genes, tissue-specifically expressed genes, viral genes, and cell cycle-regulated genes (1, 2). Sp3 contains a highly conserved DNA-binding domain close to the C terminus and two glutamine-rich activation domains in the N-terminal moiety. The expression pattern, the structure, and the DNAbinding properties of Sp3 are very similar to Sp1, which suggested originally that these two proteins exert similar functions. The physiological roles of Sp1 and Sp3, however, appear to be significantly different. Sp1 knock-out mouse embryos are severely retarded in growth, and die after day 10 of embryonic development (3). Sp3-deficient embryos develop until birth, but die invariably of respiratory failure immediately after birth (4). In addition, late tooth and bone developmental processes are impaired in Sp3Ϫ/Ϫ mice (4, 5).Functional analyses of the transcriptional properties of Sp1 and Sp3 also revealed significant differences between these two transcription factors (6). On many reporter constructs containing multiple Sp-binding sites Sp3 is, unlike Sp1, inactive or acts only as a weak activator (7). The molecular basis for the inactivity of Sp3 under these conditions has been mapped to an inhibitory domain located between the second glutamine-rich activation domain and the zinc finger region (8). More recently, it was shown that Sp3 is post-translationally modified by the small ubiquitin-like modifier (SUMO) 1 within its inhibitory domain and that SUMO modification leads to inactivation (9, 10).All previously published studies with Sp3 (more than 500 ...

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Transcription factor Sp3 is essential for post-natal survival and late tooth development

Cited by 172 publications

References 33 publications

Functional analysis of two Sp1/Sp3 binding sites in murine Nanog gene promoter

Functional analysis of two Sp1/Sp3 binding sites in murine Nanog gene promoter

The Krüppel-like Factor Epiprofin Is Expressed by Epithelium of Developing Teeth, Hair Follicles, and Limb Buds and Promotes Cell Proliferation

Complexity of Translationally Controlled Transcription Factor Sp3 Isoform Expression

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