Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis

Jen, Yale; Manova, Katia; Benezra, Robert

doi:10.1002/(sici)1097-0177(199701)208:1<92::aid-aja9>3.0.co;2-x

Cited by 195 publications

(105 citation statements)

References 50 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…During development, all members of the Id family are expressed in many organs and tissues, showing overlapping but distinct expression patterns in developmental stage-dependent and region-speci®c manners (Evans and O'Brien, 1993;Riechmann and Sablitzky, 1995;Zhu et al, 1995;Jen et al, 1996Jen et al, , 1997. This re¯ects the important roles of Id proteins in the regulation of bHLH factors' functions in normal development and di erentiation.…”

Section: Early Developmentmentioning

confidence: 99%

“…This re¯ects the important roles of Id proteins in the regulation of bHLH factors' functions in normal development and di erentiation. As demonstrated by in situ hybridization studies, a general feature of Id gene expression during development is that the distributions of Id1, Id2 and Id3 are overlapping, while Id4 shows a unique pattern during embryogenesis (Riechmann and Sablitzky, 1995;Jen et al, 1996Jen et al, , 1997. In addition, tissues that undergo epithelialmesenchymal interactions have a tendency to express Id genes, as observed in the salivary gland, kidney and lung (Evans and O'Brien, 1993;Zhu et al, 1995;Jen et al, 1996).…”

Section: Early Developmentmentioning

confidence: 99%

See 1 more Smart Citation

Id and development

2001

View full text Add to dashboard Cite

During development, it is obvious that enormous multiplication and diversi®cation of cells is required to build a body plan from a single fertilized egg and that these two processes, proliferation and di erentiation, must be coordinated properly. Id proteins, negative regulators of basic helix ± loop ± helix transcription factors, possess the ability to inhibit di erentiation and to stimulate proliferation, and are useful molecules for investigating the mechanisms regulating development. In the past few years, our understanding of the roles of Id proteins has been substantially enhanced by the detailed investigation of genetically modi®ed animals. The data have indicated that the functions of Id proteins in vivo are functionally related to those revealed by earlier work in cell culture systems. However, unexpected organs and cell types have also been found to require Id proteins for their normal development. This review looks at the advances made in our understanding of the in vivo functions of Id proteins. The topics discussed include neurogenesis, natural killer cell development, lymphoid organogenesis, mammary gland development and spermatogenesis. Oncogene (2001) 20, 8290 ± 8298

show abstract

Section: Early Developmentmentioning

confidence: 99%

Section: Early Developmentmentioning

confidence: 99%

Id and development

2001

View full text Add to dashboard Cite

show abstract

“…2005), vascular endothelial cells (Pammer et al, 2004;Kim et al, 2007), myocytes (Alway et al, 2002;Liu et al, 2002), cardiac myocytes (Ding et al, 2006b), and neuronal cells (Jen et al, 1997;Lyden et al, 1999;Nakashima et al, 2001). Id proteins, which lack a DNA binding domain, associate with other transcriptional factors and prevent them from binding DNA or forming active heterodimers (Benezra et al, 1990b).…”

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

View full text Add to dashboard Cite

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...

show abstract

“…Currently, four known human ID proteins have been identified. Expression studies in embryonic tissues showed that ID proteins play critical roles in early embryonic development (Jen et al, 1996(Jen et al, , 1997Kee and Bronner-Fraser 2001). They are also involved in angiogenesis, lymphocyte development, cell cycle control and cellular senescence as recently reviewed (Benezra et al, 2001;Rivera and Murre 2001;Zebedee and Hara 2001).…”

mentioning

confidence: 95%

“…Regarding ID4, known differences in various aspects have distinguished it from other ID members and thus lend support for its unique functional role. These differences include a more restricted expression pattern of ID4 during mouse and avian embryogenesis, which is distinct from the other three ID members (Jen et al, 1996(Jen et al, , 1997Kee and BronnerFraser, 2001). While ID1, ID2 and ID3 were expressed at very early stage of development, ID4 was expressed later in time and in tissues at more advanced stages of differentiation.…”

mentioning

confidence: 99%

Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma

et al. 2003

View full text Add to dashboard Cite

Promoter hypermethylation has become apparent as a common mechanism of gene silencing in cancer. Based on our published microarray expression data, we noticed a prominent downregulation of ID4 in gastric adenocarcinoma. The dense 5 0 CpG island covering the previously mapped upstream promoter of ID4 has prompted us to relate its downregulation to promoter hypermethylation. ID proteins are distinct members in the helix-loop-helix family of transcriptional regulators, which modulate various key developmental processes. Emerging data have suggested the involvement of ID genes in tumorigenesis. In this study using bisulfite genomic sequencing, we have found hypermethylation of ID4 promoter in most gastric cancer cell lines and 30% of primary tumors. This correlated with decreased level of ID4 expression. Restoration of ID4 expression in various gastric cancer cell lines was achieved by treatment with the DNA methyltransferase inhibitor 5-aza-2 0 -deoxycytidine, which at times required the synergistic action of the histone deacetylase inhibitor trichostatin A, but not with trichostatin A alone. Re-expression was accompanied by the corresponding ID4 promoter demethylation. Furthermore, we have found significant association of ID4 promoter methylation with hMLH1 promoter methylation (P ¼ 0.008) and microsatellite instability (P ¼ 0.006). Overall, our results have shown that transcriptional silencing of ID4 is related to the aberrant methylation of its promoter in gastric cancer. The significant association of ID4 and hMLH1 promoter hypermethylation suggested that ID4 may also be among the genes being targeted in the CpG island methylator phenotype tumorigenic pathway.

show abstract

Each member of the Id gene family exhibits a unique expression pattern in mouse gastrulation and neurogenesis

Cited by 195 publications

References 50 publications

Id and development

Id and development

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

Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma

Contact Info

Product

Resources

About