Abstract
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.
Highlights
IntroductionMouse Dermo-1 is a member of the basic helix-loop-helix (bHLH) transcription factor family that was initially isolated using the yeast two-hybrid system with the bHLH domain of ubiquitously expressed E12 as bait [1]
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, basic helix-loop-helix (bHLH), and C-terminal structural domains in transcriptional repression
Mouse Dermo-1 is a member of the basic helix-loop-helix1 transcription factor family that was initially isolated using the yeast two-hybrid system with the bHLH domain of ubiquitously expressed E12 as bait [1]
Summary
Mouse Dermo-1 is a member of the basic helix-loop-helix (bHLH) transcription factor family that was initially isolated using the yeast two-hybrid system with the bHLH domain of ubiquitously expressed E12 as bait [1]. 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. Twist, sharing significant homology with Dermo-1, contains both basic and HLH domains and has been shown to be a potent transcriptional repressor for MyoD [1, 27]. The repression mechanisms of Twist on MyoD transactivation have been demonstrated to be mediated by direct interaction with the basic domain of MyoD, sequestering E proteins, inhibiting MEF2 activation, and inhibiting the histone acetylase activity of MyoD coactivators such as pCAF and CBP (28 –30)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
