Lecture3 Paper2 - Fig 7B A Model for the Role of HDACs in...

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Unformatted text preview: Fig. 7B: A Model for the Role of HDACs in Skeletal Myogenesis B. In myoblasts, HDAC binds MEF2 and represses muscle gene expression. CaMK signaling and MAPK (MKK6) signaling stimulate myogenesis by enhancing MEF2 activity (IGF is involved in activating CaMK). IGF Paper #2: Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation, T.A. McKinsey, C. Zhang, J. Lu, and E.N. Olson, Nature, 408: 106-111, 2000. (cited 384 times; Impact Factor 34) Question: What is the subcellular distribution of HDACs and MEF2 during skeletal myogenesis? Hypothesis: The subcellular distribution of HDACs regulate their ability to inhibit skeletal myogenesis a = Importin a, b = Importin b, NPC = Nuclear pore complex, NLS = Nuclear localization sequence QuickTime™ and a decompressor are needed to see this picture. http://sspatel.googlepages.com/nuclearporecomplex Nuclear Import Movie Nuclear export is inhibited by Leptomycin B (LMB) NES=Nuclear Export Signal Crm1 = chromosome region maintenance protein 1 Nucleus Nucleus Cytoplasm Does HDAC shuttle between the nucleus and cytoplasm? Found: • HDAC moves from the nucleus to the cytoplasm in differentiating myotubes • MEF2A/C remains predominantly nuclear Therefore, the ability of HDAC to inhibit myogenesis may be regulated by controlling its subcellular localization. Fig. 1. Shuttling of HDAC5 from the nucleus to the cytoplasm during myogenesis – Immunofluorescence of HDAC5 and MEF2A/C in C2 myoblasts * Fig. 2 HDAC5 is excluded from the nucleus in cells expressing activated forms of CaMK. Found: • Activated CamKI or IV expression results in the translocation of HDAC5 into the cytoplasm, but not HDAC1 or 3 • MEF2C remains nuclear * Fig. 2 HDAC5 is excluded from the nucleus in cells expressing activated forms of CaMK....
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This note was uploaded on 12/18/2011 for the course BCH 4122 taught by Professor Ilonaskerjanc during the Spring '11 term at University of Ottawa.

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Lecture3 Paper2 - Fig 7B A Model for the Role of HDACs in...

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