Browsing by Subject "histone deacetylases"

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    Class I histone deacetylases in retinal progenitors and differentiating ganglion cells
    (Elsevier, 2018-12) Saha, Ankita; Tiwari, Sarika; Dharmarajan, Subramanian; Otteson, Deborah C.; Belecky-Adams, Teri L.; Biology, School of Science
    Background The acetylation state of histones has been used as an indicator of the developmental state of progenitor and differentiating cells. The goal of this study was to determine the nuclear localization patterns of Class I histone deacetylases (HDACs) in retinal progenitor cells (RPCs) and retinal ganglion cells (RGCs), as the first step in understanding their potential importance in cell fate determination within the murine retina. Results The only HDAC to label RPC nuclei at E16 and P5 was HDAC1. In contrast, there was generally increased nuclear localization of all Class I HDACs in differentiating RGCs. Between P5 and P30, SOX2 expression becomes restricted to Müller glial, cholinergic amacrine cells, and retinal astrocytes. Cholinergic amacrine showed a combination of changes in nuclear localization of Class I HDACs. Strikingly, although Müller glia and retinal astrocytes express many of the same genes, P30 Müller glial cells showed nuclear localization only of HDAC1, while retinal astrocytes were positive for HDACs 1, 2, and 3. Conclusion These results indicate there may be a role for one or more of the Class I HDACs in retinal cell type-specific differentiation.
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    HDAC1 and HDAC2 Control the Specification of Neural Crest Cells into Peripheral Glia
    (Society for Neuroscience, 2014-04-23) Jacob, Claire; Lötscher, Pirmin; Engler, Stefanie; Baggiolini, Arianna; Tavares, Sandra Varum; Brügger, Valérie; John, Nessy; Büchmann-Møller, Stine; Snider, Paige L.; Conway, Simon J.; Yamaguchi, Teppei; Matthias, Patrick; Sommer, Lukas; Mantei, Ned; Suter, Ueli; Department of Pediatrics, School of Medicine
    Schwann cells, the myelinating glia of the peripheral nervous system (PNS), originate from multipotent neural crest cells that also give rise to other cells, including neurons, melanocytes, chondrocytes, and smooth muscle cells. The transcription factor Sox10 is required for peripheral glia specification. However, all neural crest cells express Sox10 and the mechanisms directing neural crest cells into a specific lineagearepoorlyunderstood.Weshowherethathistonedeacetylases1and2(HDAC1/2)areessentialforthespecificationofneuralcrest cells into Schwann cell precursors and satellite glia, which express the early determinants of their lineage myelin protein zero (P0) and/or fatty acid binding protein 7 (Fabp7). In neural crest cells, HDAC1/2 induced expression of the transcription factor Pax3 by binding and activating the Pax3 promoter. In turn, Pax3 was required to maintain high Sox10 levels and to trigger expression of Fabp7. In addition, HDAC1/2 were bound to the P0 promoter and activated P0 transcription. Consistently, in vivo genetic deletion of HDAC1/2 in mouse neuralcrestcellsledtostronglydecreasedSox10expression,nodetectablePax3,virtuallynosatelliteglia,andnoSchwanncellprecursors in dorsal root ganglia and peripheral nerves. Similarly, in vivo ablation of Pax3 in the mouse neural crest resulted in strongly reduced expression of Sox10 and Fabp7. Therefore, by controlling the expression of Pax3 and the concerted action of Pax3 and Sox10 on their target genes, HDAC1/2 direct the specification of neural crest cells into peripheral glia.