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HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells. Nature Neuroscience, 14, 429-436

Institute of Cell Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.
Nature Neuroscience (Impact Factor: 16.1). 03/2011; 14(4):429-36. DOI: 10.1038/nn.2762
Source: PubMed

ABSTRACT

Histone deacetylases (HDACs) are major epigenetic regulators. We show that HDAC1 and HDAC2 functions are critical for myelination of the peripheral nervous system. Using mouse genetics, we have ablated Hdac1 and Hdac2 specifically in Schwann cells, resulting in massive Schwann cell loss and virtual absence of myelin in mutant sciatic nerves. Expression of Sox10 and Krox20, the main transcriptional regulators of Schwann cell myelination, was greatly reduced. We demonstrate that in Schwann cells, HDAC1 and HDAC2 exert specific primary functions: HDAC2 activates the transcriptional program of myelination in synergy with Sox10, whereas HDAC1 controls Schwann cell survival by regulating the levels of active β-catenin.

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Available from: Dies Meijer, Mar 29, 2014
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    • "Likewise, dual HDAC1/2 ablation resulted in apoptotic megakaryocytes, anemia and thrombocytopenia in the hematopoietic system (Wilting et al. 2010; Yamaguchi et al. 2010), hyperacetylation of TRP53 followed by apoptosis in oocytes (Ma et al. 2012), mitotic failure in proliferating hepatocytes (Xia et al. 2013) or decreased autophagy in skeletal muscles (Moresi et al. 2012). Upon simultaneous HDAC1/2 deletion in Schwann cells, myelin deficiency and massive cell loss were observed and attributed at least in part to hyperacetylation of NF-κB (Chen et al. 2011; Jacob et al. 2011). "

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    • "The highly homologous class I deacetylases HDAC1 and HDAC2 can homo-and hetero-dimerize and are components of the Sin3, NuRD, CoREST and NODE co-repressor complexes (reviewed in Brunmeir et al, 2009). Loss-of-function studies in the mouse suggest partial functional redundancy for these enzymes in different cell types and tissues (Montgomery et al, 2007; Yamaguchi et al, 2010; Chen et al, 2011; Jacob et al, 2011; Ma et al, 2012). Recently, LeBoeuf et al (2011) have shown that HDAC1 and HDAC2 play a central role in embryonic ectoderm development. "
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    • "Likewise, dual HDAC1/2 ablation resulted in apoptotic megakaryocytes, anemia and thrombocytopenia in the hematopoietic system (Wilting et al. 2010; Yamaguchi et al. 2010), hyperacetylation of TRP53 followed by apoptosis in oocytes (Ma et al. 2012), mitotic failure in proliferating hepatocytes (Xia et al. 2013) or decreased autophagy in skeletal muscles (Moresi et al. 2012). Upon simultaneous HDAC1/2 deletion in Schwann cells, myelin deficiency and massive cell loss were observed and attributed at least in part to hyperacetylation of NF-κB (Chen et al. 2011; Jacob et al. 2011). "
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