Human dermo-1 has attributes similar to twist in early bone development

Lee, M.S; Lowe, Gina; Flanagan, Steven D.; Kuchler, Karl; Glackin, Carlotta A.

doi:10.1016/s8756-3282(00)00380-x

Cited by 71 publications

(57 citation statements)

References 38 publications

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“…In the present study, we demonstrate that overexpressing Twist-1 and Dermo-1 MSC lines undergo a change in cell phenotype characteristic of immature osteogenic progenitor populations, as previously described for human osteosarcoma cell lines [11,13]. These observations were based on high cell surface expression of the mesenchymal precursor marker, STRO-1, and lower levels of the osteoblast associated marker, alkaline phosphatase [26].…”

Section: Discussionsupporting

confidence: 85%

“…One family of genes involved in early development comprises the TWIST family members, Twist-1 (Twist) and Twist-2 (Dermo-1), which encode for basic helix-loop-helix (bHLH) containing transcription factors [10][11][12][13]. In situ analysis of murine embryonic development has provided evidence that Twist-1 is downregulated during endochondral and intramembranous fetal bone development [14].…”

Section: Introductionmentioning

confidence: 99%

“…[15,16]. Twist family members and other bHLH factors, including scleraxis and paraxis, have been found to be crucial for correct patterning of the skeleton [11,13,17,18]. The bHLH factors act by first homo-or heterodimerizing with other bHLH molecules, and subsequently binding to a conserved motif known as the E box (CANNTG), which leads to either activation or inhibition of transcription [19].…”

Section: Introductionmentioning

confidence: 99%

“…Glackin and colleagues reported that enforced expression of either Twist-1 or Twist-2 in human osteosarcoma cell lines inhibited their ability to undergo osteoblastic maturation, whereas overexpression of Twist-1 or Dermo-1 antisense increased bone cell maturation [11,13]. These findings led us to become interested in the role of bHLH in stem cell maintenance because of the potential for translating this knowledge into methods of optimizing the number of adult stem cells.…”

Section: Introductionmentioning

confidence: 99%

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TWIST Family of Basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stem Cell Growth and Commitment

et al. 2009

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The TWIST family of basic helix-loop-helix transcription factors, Twist-1 and Dermo-1 are known mediators of mesodermal tissue development and contribute to correct patterning of the skeleton. In this study, we demonstrate that freshly purified human bone marrow-derived mesenchymal stromal/stem cells (MSC) express high levels of Twist-1 and Dermo-1 which are downregulated following ex vivo expansion. Enforced expression of Twist-1 or Dermo-1 in human MSC cultures increased expression of the MSC marker, STRO-1, and the early osteogenic transcription factors, Runx2 and Msx2. Conversely, overexpression of Twist-1 and Dermo-1 was associated with a decrease in the gene expression of osteoblast-associated markers, bone morphogenic protein-2, bone sialoprotein, osteopontin, alkaline phosphatase and osteocalcin. High expressing Twist-1 or Dermo-1 MSC lines exhibited an enhanced proliferative potential of approximately 2.5-fold compared with control MSC populations that were associated with elevated levels of Id-1 and Id-2 gene expression. Functional studies demonstrated that high expressing Twist-1 and Dermo-1 MSC displayed a decreased capacity for osteo/chondrogenic differentiation and an enhanced capacity to undergo adipogenesis. These findings implicate the TWIST gene family members as potential mediators of MSC self-renewal and lineage commitment in postnatal skeletal tissues by exerting their effects on genes involved in the early stages of bone development.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TWIST Family of Basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stem Cell Growth and Commitment

et al. 2009

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“…During embryogenesis, this gene is predominantly expressed in mesodermal-and ectodermal-derived tissues including somites, dermis, chondroblasts, limbs, teeth, and cranial structures and is believed to play important roles in the development and differentiation of these tissues and organs. Homologs of mouse Dermo-1 have been found in several other vertebrates such as humans, rats, and chicks with extensive sequence conservation during evolution (2)(3)(4). Interestingly, Dermo-1 homologs are also expressed in a subset of mesodermal-and ectodermal-derived tissues such as subectodermal mesenchyme, osteoblasts, and limb buds (2)(3)(4), which potentially act as negative regulators of differentiation.…”

mentioning

confidence: 99%

Dermo-1, a Multifunctional Basic Helix-Loop-Helix Protein, Represses MyoD Transactivation via the HLH Domain, MEF2 Interaction, and Chromatin Deacetylation

Gong

2002

Journal of Biological Chemistry

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Dermo-1 is a multifunctional basic helix-loop-helix (bHLH) transcription factor that has been shown to be a potent negative regulator for gene transcription and apoptosis. To understand the molecular mechanisms that mediate the function of Dermo-1, we generated a series of Dermo-1 mutants and used a MyoD-mediated transcriptional activation model to characterize the roles of its N-terminal, bHLH, and C-terminal structural domains in transcriptional repression. Both the C-terminal and HLH domains of Dermo-1 were essential for its repression of MyoD-mediated transactivation. Dermo-1 repressed, in a dose-dependent fashion, the transactivation activity of myocyte enhancer factor 2 (MEF2), a protein known to cooperate with MyoD in activating E-box-dependent gene expression. Both the N-and C-terminal domains of Dermo-1, but not the bHLH domain, were required for the inhibition of MEF2, suggesting that Dermo-1 inhibits both MyoD-and MEF2-dependent transactivation but through different mechanisms. Dermo-1 interacted directly with MEF2 and selectively repressed the MEF2 transactivation domain. An overall increase of histone acetylation induced by trichostatin A treatment reduced Dermo-1 transcriptional repression activity, suggesting that histone deacetylation is involved in Dermo-1-mediated transcriptional repression. Together, these results suggest that MEF2 is an important target in Dermo-1-mediated transcriptional repression and provide initial evidence of the involvement of histone acetylation in Dermo-1 transcriptional repression.

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A survey ofTWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals

Elanko¹,

Sibbring

Metcalfe

et al. 2001

Hum. Mutat.

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The human TWIST gene encodes a 202 amino acid transcription factor characterized by a highly conserved basic-helix-loop-helix motif in the C-terminal half, and a less conserved N-terminal half that has binding activity toward the histone acetyltransferase p300. Between these domains is a repeat region of unknown function that encodes the glycine-rich sequence (Gly)5Ala(Gly)5. Heterozygous mutations of TWIST were previously described in Saethre-Chotzen craniosynostosis syndrome [El Ghouzzi et al., 1997; Howard et al., 1997]. During a search for TWIST mutations in patients with craniosynostosis, we identified, in addition to 11 novel and one previously described bona fide mutations, several individuals with rearrangements of the glycine-rich region, involving either deletion of 18 nucleotides or insertion of three, 15, or 21 nucleotides. None of these rearrangements was consistently associated with clinical disease and we conclude that they are at most weakly pathogenic. The glycine stretch may serve as a flexible linker between the functional domains of the TWIST protein, and as such may be subject to reduced evolutionary constraint.

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Human dermo-1 has attributes similar to twist in early bone development

Cited by 71 publications

References 38 publications

TWIST Family of Basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stem Cell Growth and Commitment

TWIST Family of Basic Helix-Loop-Helix Transcription Factors Mediate Human Mesenchymal Stem Cell Growth and Commitment

Dermo-1, a Multifunctional Basic Helix-Loop-Helix Protein, Represses MyoD Transactivation via the HLH Domain, MEF2 Interaction, and Chromatin Deacetylation

A survey ofTWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals

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