Characterization of the Human Bone SialoProtein (BSP) Gene and its Promoter Sequence

Kim, Richard H.; Shapiro, Howard S.; Li, Jack J.; Wrana, Jeffrey L.; Sodek, Jaro

doi:10.1016/0945-053x(94)90027-2

Cited by 97 publications

(90 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These genes are periostin (Postn, previously named osteoblast-specific factor 2 or Osf2) (70 -72), the procollagen A1␣1 gene (Col1a1) (73)(74)(75)(76), and the bone sialoprotein gene (BSP) (77,78). The mRNA levels of Col1a1 and Postn were examined by Northern blot analyses in the three Hoxa1 ES cell lines and in AB1 ES cells in order to validate our microarray results.…”

Section: Expression Of Polycomb Group Genes In the Emc-eshoxa1-15mentioning

confidence: 99%

Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

Martinez‐Ceballos

Chambon

Gudas

2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Homeobox (Hox) genes encode a family of transcription factors that regulate embryonic patterning and organogenesis. In embryos, alterations of the normal pattern of Hox gene expression result in homeotic transformations and malformations. Disruption of the Hoxa1 gene, the most 3 member of the Hoxa cluster and a retinoic acid (RA) direct target gene, results in abnormal ossification of the skull, hindbrain, and inner ear deficiencies, and neonatal death. We have generated Hoxa1 genes positioned at the 3Ј-end are expressed earlier and more anterior, whereas 5Ј-end genes are expressed at later times and more posterior (reviewed in Refs. 1 and 5). Colinear gene expression from these Hox gene clusters may involve an initial change in chromatin structure (histone modification and chromatin decondensation) of the entire loci, which would then facilitate the programmed expression of genes along the clusters by a progressive 3Ј to 5Ј change in higher order chromatin structure (6). Treatment of teratocarcinoma cells or embryonic stem cells with retinoic acid (RA), which acts via the retinoic acid receptors (RAR␣, -␤, and -␥ and their isoforms (reviewed in Refs. 7 and 8), results in the sequential activation of several Hox genes in a manner that resembles their positions in the clusters, e.g. 3Ј genes are activated before 5Ј genes (7-9). Moreover, our laboratory discovered the presence of a retinoic acid response element (RARE) in the 3Ј enhancer of the Hoxa1 gene (10 -13). This RARE is also functional in transgenic mice (14 -16). We also demonstrated that unlike F9 Wt cells, F9 RAR␥ Ϫ/Ϫ cells fail to express the Hoxa1 gene in response to RA (17). Alterations in the normal pattern of Hox gene expression in embryos result in homeotic transformations and malformations, and frequently, in perinatal lethality (3,18). For instance, the targeted inactivation in mice of both alleles of the most 3Ј member of the Hoxa cluster, the Hoxa1 gene, leads to numerous developmental defects, including hindbrain deficiencies and abnormal skull ossification, and ultimately, to neonatal death (19 -22). Numerous studies have demonstrated that the hindbrain defects in Hoxa1 Ϫ/Ϫ mice result in part from the failure of Hoxb1 to reach its anterior limit of expression at the presumptive rhombomere 3/rhombomere 4 (r3/4) boundary, which initiates a cascade of gene misexpression that results in the misspecification of the hindbrain compartments from r2 to r5 (23-26). Furthermore, the ectopic expression of Hoxa1 in transgenic mice leads to the ectopic activation of Hoxb1 in r2, produces anterior abnormalities, including the reorganization of the developing hindbrain, and ultimately results in embryonic death (27). These observations highlight the importance of the Hoxa1 gene and suggest that the regulatory effects of retinoids on cell growth and on embryonic patterning may be * This work was supported by National Institutes of Health Grants R01CA43796 (to L. J. G.) and UR 2U19HDO35466. The costs of publication of this article were defrayed in part by th...

show abstract

Section: Expression Of Polycomb Group Genes In the Emc-eshoxa1-15mentioning

confidence: 99%

Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

Martinez‐Ceballos

Chambon

Gudas

2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Smad6 can be recruited as a co-repressor with the Hoxc8 protein (Bai et al, 2000). Homeobox binding sites have been reported in the promoters of a number of osteoblast-expressed genes, including the NCAM (Boersma et al, 1999), bone sialoprotein (Kim et al, 1994;Li and Sodek, 1993), and osteocalcin genes (Towler et al, 1994). Activity of the rat osteocalcin gene promoter has been shown to be dependent on the homeobox binding motif (Hoffmann et al, 1996;Towler et al, 1994).…”

Section: Regulation Of Maintenance and Remodeling In Cartilage And Bomentioning

confidence: 99%

Molecular basis for skeletal variation: insights from developmental genetic studies in mice

Kappen

Neubüser

Balling

et al. 2007

Birth Defects Research Pt B

View full text Add to dashboard Cite

Skeletal variations are common in humans, and potentially are caused by genetic as well as environmental factors. We here review molecular principles in skeletal development to develop a knowledge base of possible alterations that could explain variations in skeletal element number, shape or size. Environmental agents that induce variations, such as teratogens, likely interact with the molecular pathways that regulate skeletal development. Birth Defects Res (Part B), 80:425–450, 2007. © 2007 Wiley‐Liss, Inc.

show abstract

“…Thus, regulation of BSP gene transcription appears to be important in the differentiation of osteoblasts, for bone matrix mineralization and for pathologic mineralization. To study the transcriptional regulation of BSP gene expression, we and other groups have cloned and sequenced the rat, human and mouse BSP gene promoters (17)(18)(19), which are highly conserved within a 370 bp proximal region. This region includes an inverted TATA box (20) overlapping a vitamin D response element (21) and an inverted CCAAT box (−50 to −46), which is required for basal transcriptional activity (22,23).…”

Section: Introductionmentioning

confidence: 99%

<b>Effects of Thalidomide on Bone Sialoprotein Gene Transcription </b>

et al. 2015

View full text Add to dashboard Cite

Thalidomide is an immunomodulatory drug and primarily prescribed as a sedative and hypnotic. Treatment with thalidomide inhibited osteoblast development. Bone sialoprotein (BSP) is a mineralized tissue-specific protein that appears to function in the initial mineralization of bone. BSP expression is essentially restricted to differentiated cells of mineralized connective tissues and that the expression of BSP is developmentally regulated. To determine molecular mechanisms involved in the suppression of bone formation we have analyzed the effects of thalidomide on BSP gene expression.Thalidomide (10 μg/ml) decreased BSP mRNA levels at 12 h in ROS 17/2.8 osteoblast-like cells. Transient transfection analyses, using chimeric constructs of the rat BSP gene promoter linked to a luciferase reporter gene, revealed that thalidomide (10 μg/ml, 12 h) suppressed luciferase activities of pLUC3 (nts −116 to +60), pLUC4 (nts −425 to +60) and pLUC5 (nts −801 to +60) transfected into ROS17/2.8 cells. Further deletion analysis of the BSP promoter showed that a region within nts −43 to −84 was targeted by thalidomide. Introduction of 2 bp mutations in the inverted CCAAT box (ATTGG; nts −50 and −46), a putative cAMP response element (CRE; nts −75 to −68), a fibroblast growth factor 2 (FGF2) response element (FRE; nts −92 to −85) and a pituitary-specific transcription factor-1 (Pit-1) binding site (Pit-1; nts −111 to −105) showed that the thalidomide effects were mediated by the CRE and inverted CCAAT box. Gel mobility shift analyses showed that thalidomide increased nuclear protein binding to CRE. Whereas, inverted CCAAT box binding proteins did not change after stimulation by thalidomide.Antibodies against CRE-binding protein 1 (CREB1), phospho-CREB1, c-Fos, c-Jun, JunD and CREB2 disrupted CRE-protein complex formation. These studies, therefore, demonstrated that thalidomide suppresses BSP gene transcription mediated by CRE and inverted CCAAT box in the rat BSP gene promoter.

show abstract

Characterization of the Human Bone SialoProtein (BSP) Gene and its Promoter Sequence

Cited by 97 publications

References 38 publications

Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

Molecular basis for skeletal variation: insights from developmental genetic studies in mice

<b>Effects of Thalidomide on Bone Sialoprotein Gene Transcription </b>

Contact Info

Product

Resources

About