The 2.2-kb promoter of cartilage-derived retinoic acid-sensitive protein controls gene expression in cartilage and embryonic mammary buds of transgenic mice

Xie, Wei-Fen; Zhang, Xin; Sandell, Linda J.

doi:10.1016/s0945-053x(00)00087-1

Cited by 25 publications

(36 citation statements)

References 36 publications

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“…Even though the levels of type II collagen appeared to be less than that in the growth plate ( Figures 2B and 2G), the distribution was coincident with toluidine blue (Figures 2A and 2E). We have previously shown that CD-RAP protein can be detected intracellularly in the articular surface and meniscus of an 8-week mouse (Xie et al 2000). Using dithiothreitol to aid in matrix detection, here we show that CD-RAP deposition in both the articular and meniscal cartilages is very low ( Figure 2I).…”

Section: Articular and Meniscal Cartilagesupporting

confidence: 49%

Distribution of the Transcription Factors Sox9, AP-2, and [Delta]EF1 in Adult Murine Articular and Meniscal Cartilage and Growth Plate

Davies

Sakano

Zhu

et al. 2002

J Histochem Cytochem.

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the development, maintenance, and repair of cartilage tissues. Matrix molecule synthesis is generally regulated by the rate of gene transcription determined by DNA transcription factors. We have shown that transcription factors Sox9, AP-2, and [delta]EF1 are able to alter the rate of CD-RAP transcription in vitro: Sox9 upregulates, AP-2 exhibits biphasic effects, and [delta]EF1 represses expression of the CD-RAP gene. To correlate these in vitro activities in vivo, transcription factors were co-immunolocalized with ECM proteins in three different cartilage tissues in which the rates of biosynthesis are quite different: articular, meniscal, and growth plate. Immunoreactivities of type II collagen and CD-RAP were higher in growth plate than in either the articular or meniscal cartilages and correlated positively with Sox9 protein. Sox9 staining decreased with hypertrophy and was low in articular and meniscal cartilages. In contrast, AP-2 and [delta]EF1 were low in proliferating chondrocytes but high in lower growth plate, articular, and meniscal cartilages. This increase was also accompanied by intense nuclear staining. These immunohistochemical results are the first to localize both [delta]EF1 and AP-2 to adult articular, meniscal, and growth plate cartilages and provide in vivo correlation of previous molecular biological studies.

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Section: Articular and Meniscal Cartilagesupporting

confidence: 49%

Distribution of the Transcription Factors Sox9, AP-2, and [Delta]EF1 in Adult Murine Articular and Meniscal Cartilage and Growth Plate

Davies

Sakano

Zhu

et al. 2002

J Histochem Cytochem.

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“…9A) encoding truncated Cbfa1 proteins in mammalian cells (generously provided by Drs. K. Ito and Y.Toshiyuki) (14). Pull-down assays involving the immobilized GST-204 and cell extracts prepared from HEK293 cells transfected with various Cbfa1 deletion mutants (Fig.…”

Section: P204 Acts As the Coactivator Of Cbfa1mentioning

confidence: 99%

“…The molecular mechanisms underlying the pathogenesis of cleidocranial dysplasia are not completely defined. Some mutants of Cbfa1 abolish its DNAbinding activity (10 -12), and others disturb the associations of Cbfa1 to its binding partners, including Smads (14). It was found that several Cbfa1-binding proteins, such as retinoblastoma protein (pRb) (15) and core-binding factor-␤ (Cbfb) (16,17) may also play critical roles in bone development.…”

mentioning

confidence: 99%

The Interferon-inducible p204 Protein Acts as a Transcriptional Coactivator of Cbfa1 and Enhances Osteoblast Differentiation

Liu

Chang

Jin

et al. 2005

Journal of Biological Chemistry

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The differentiation of uncommitted mesenchymal cells into osteoblasts is a fundamental molecular event governing both embryonic development and bone repair. The bone morphogenetic proteins (BMPs) are important regulators of this process; they function by binding to cell surface receptors and signaling by means of Smad proteins. Core binding factor ␣-1 (Cbfa1), a member of the runt family of transcription factors, is an essential transcriptional regulator of osteoblast differentiation and bone formation, and this process is positively or negatively regulated by a variety of coactivators and corepressors. We report that p204, an interferon-inducible protein that was previously shown to inhibit cell proliferation and promote the differentiation of myoblasts to myotubes, is a novel regulator in the course of osteogenesis. p204 is expressed in embryonic osteoblasts and hypertrophic chondrocytes in the growth plate as well as in the calvaria osteoblasts of neonatal mice. Its level is increased in the course of the BMP-2-triggered osteoblast differentiation of pluripotent C2C12 cells. This increase is probably due to the activation of the gene encoding 204 (Ifi204) by Smad transcription factor, including Smad1, -4, and -5. Overexpression of p204 enhances the BMP-2-induced osteoblast differentiation in vitro, as revealed by elevated alkaline phosphatase activity and osteocalcin production. p204 acts as a cofactor of Cbfa1: 1) high levels of p204 augment, whereas the lowering of p204 level decreases, the Cbfa1-dependent transcription, and 2) p204 associates with Cbfa1 both in vitro and in vivo. Two nonoverlapping segments in p204 bind to Cbfa1, and the N-terminal 88-amino acid segment of Cbfa1 is required for binding to p204. p204, which is the first interferoninducible protein found to associate with Cbfa1, functions as a novel regulator of osteoblast differentiation.

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“…The molecular mechanisms underlying the pathogenesis of CCD are not completely defined. Some mutations of Cbfa1 abolish its DNA binding activity (Lee et al, 1997;Zhou et al, 1999) and others disturb the association of Cbfa1 to its binding partners, including Smads (Xie et al, 2000). It was found that several Cbfa1-binding proteins such as retinoblastoma protein (pRb) (Thomas et al, 2001), p204 (Liu et al, 2005), and Core binding factor ␤ (Kundu et al, 2002;Yoshida et al, 2002) may also play critical roles in bone development.…”

Section: Introductionmentioning

confidence: 99%

p204 Protein Overcomes the Inhibition of Core Binding Factor α-1–mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins

Luan

Yang

et al. 2008

MBoC

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Id proteins play important roles in osteogenic differentiation; however, the molecular mechanism remains unknown. In this study, we established that inhibitor of differentiation (Id) proteins, including Id1, Id2, and Id3, associate with core binding factor ␣-1 (Cbfa1) to cause diminished transcription of the alkaline phosphatase (ALP) and osteocalcin (OCL) gene, leading to less ALP activity and osteocalcin (OCL) production. Id acts by inhibiting the sequence-specific binding of Cbfa1 to DNA and by decreasing the expression of Cbfa1 in cells undergoing osteogenic differentiation. p204, an interferon-inducible protein that interacts with both Cbfa1 and Id2, overcame the Id2-mediated inhibition of Cbfa1-induced ALP activity and OCL production. We show that 1) p204 disturbed the binding of Id2 to Cbfa1 and enabled Cbfa1 to bind to the promoters of its target genes and 2) that p204 promoted the translocation from nucleus to the cytoplasm and accelerated the degradation of Id2 by ubiquitin-proteasome pathway during osteogenesis. Nucleus export signal (NES) of p204 is required for the p204-enhanced cytoplasmic translocation and degradation of Id2, because a p204 mutant lacking NES lost these activities. Together, Cbfa1, p204, and Id proteins form a regulatory circuit and act in concert to regulate osteoblast differentiation. INTRODUCTIONThe differentiation of uncommitted mesenchymal cells to osteoblasts is a fundamental process in embryonic development and bone repair. The bone morphogenetic proteins (BMPs) are important regulators of this process (Heldin et al., 1997;Miyazono et al., 2000). They function by binding cell surface receptors; signaling by Smad proteins; and activating bone-specific genes, including core binding factor ␣-1 (Cbfa1) (Ducy, 2000;Miyazono et al., 2001;Attisano and Wrana, 2002). This process is positively or negatively regulated by a variety of coactivators and corepressors (Ducy et al., 2000;Miyazono et al., 2001;Attisano and Wrana, 2002). Cbfa1, also known as Runx2, PeBP2␣A, Osf2, or AML3, is a member of the runt family of transcription factors. It is an essential transcription factor of osteoblast and bone formation (Ducy, 2000). During skeletal development, Cbfa1 is observed first in early mesenchymal condensations, and it is then principally expressed in osteoblasts . Cbfa1 Ϫ/Ϫ mice exhibit a complete lack of ossification, and they die immediately after birth (Komori et al., 1997). Cbfa1 maintains osteoblastic function by regulating the expression of several bone-specific genes such as osteopontin and osteocalcin and by controlling bone extracellular matrix deposition (Ducy, 2000). Mutations in Cbfa1 are found in 65-80% of individuals with cleidocranial dysplasia (CCD) (Lee et al., 1997;Mundlos and Olsen, 1997;Zhou et al., 1999). The molecular mechanisms underlying the pathogenesis of CCD are not completely defined. Some mutations of Cbfa1 abolish its DNA binding activity (Lee et al., 1997;Zhou et al., 1999) and others disturb the association of Cbfa1 to its binding partners, including Sma...

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The 2.2-kb promoter of cartilage-derived retinoic acid-sensitive protein controls gene expression in cartilage and embryonic mammary buds of transgenic mice

Cited by 25 publications

References 36 publications

Distribution of the Transcription Factors Sox9, AP-2, and [Delta]EF1 in Adult Murine Articular and Meniscal Cartilage and Growth Plate

Distribution of the Transcription Factors Sox9, AP-2, and [Delta]EF1 in Adult Murine Articular and Meniscal Cartilage and Growth Plate

The Interferon-inducible p204 Protein Acts as a Transcriptional Coactivator of Cbfa1 and Enhances Osteoblast Differentiation

p204 Protein Overcomes the Inhibition of Core Binding Factor α-1–mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins

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