Down-Regulation of Transcription Factors AP-1, Sp-1, and NF-kappaB Precedes Myocyte Differentiation

Authors: Lehtinen S.K.¹; Rahkila P.²; Helenius M.¹; Korhonen P.³; Salminen A.²

Source: Biochemical and Biophysical Research Communications, Volume 229, Number 1, December 1996 , pp. 36-43(8)

Publisher: Academic Press

Abstract:

Terminal differentiation of myocytes involves withdrawal from the cell cycle, induction of myogenin expression, and finally formation of myotubes. To study the factors that regulate the initial phase of muscle differentiation, we analyzed the binding activities of transcription factors AP-1, Sp-1, and NF-kappaB in L6, C2C12, and rhabdomyosarcoma BA-Han-1C cells. Temporal changes in transcription factor binding activities were compared to the activation of myogenin promoter-driven CAT reporter gene and the expression level of myogenin, a master gene of myogenic differentiation. We observed a prominent decrease in the nuclear binding activities of AP-1, Sp-1, and NF-kappaB already 12 to 24 h after the transfer of cells to differentiation medium. The response was very similar in L6 and C2C12 myocytes and in BA-Han-1C rhabdomyosarcoma cells. The down-regulation clearly preceded the activation of myogenin promoter and the induction of myogenin and retinoblastoma expression, as well as the initiation of myocyte fusion. Cholera toxin and okadaic acid, established inhibitors of myogenin expression and muscle differentiation, strongly up-regulated the binding activities of AP-1, Sp-1, and NF-kappaB in differentiation medium. Myogenin expression and myocyte fusion were also inhibited. Levels of nuclear c-Fos and c-Jun proteins, components of the AP-1 complex, showed a prominent decrease already after 12 h in differentiation medium. These results show that the down-regulation of the proliferation-promoting transcription factors is a prerequisite to the initiation of myocyte differentiation.

Language: English

Document Type: Research article

Affiliations: 1: Department of Cell Biology, University of Jyvaskyla, Jyvaskyla, FIN-40351 2: Peurunka-Medical Rehabilitation and Physical Exercise Centre, Laukaa, FIN-41350 3: Department of Neuroscience and Neurology, University of Kuopio, Kuopio, FIN-70211, Finland

Publication date: 1996-12-01

• In this: publication
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• In this Subject: Anatomy & Physiology ,  Biology ,  Biochemistry
• By this author: Lehtinen S.K. ;  Rahkila P. ;  Helenius M. ;  Korhonen P. ;  Salminen A.

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