Histone deacetylase expression patterns in developing murine optic nerve.
Histone deacetylase expression patterns in developing murine optic nerve.
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DOI：
10.1186/1471-213x-14-30
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发表时间：
2014-07-09
影响因子：
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通讯作者：
Belecky-Adams TL
中科院分区：
文献类型：
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作者：
Tiwari S;Dharmarajan S;Shivanna M;Otteson DC;Belecky-Adams TL
组蛋白脱乙酰酶(HDAC)在神经胶质细胞发育和中枢神经系统多个区域的疾病状态中发挥重要作用。然而，人们对HDAC在视神经中的表达或功能知之甚少。作为了解HDACs在视神经中作用的第一步，本研究检测了甲基化的组蛋白3(K9)、乙酰化组蛋白3(K18)以及HDACs 1-6和8-11在发育中的小鼠视神经头中的时空表达模式。应用RT-qPCR、免疫印迹和免疫荧光技术分析了3个时期：胚胎第16天(E16)视柄内可见星形胶质细胞前体，出生后第5天(P5)视神经内可见未成熟的星形胶质细胞和少突胶质细胞，30天视神经星形胶质细胞和少突胶质细胞成熟。乙酰化组蛋白H3和甲基化组蛋白H3共同定位于视神经头和邻近视神经中SOX2阳性神经胶质细胞的胞核。在小鼠视神经发育的三个阶段，HDACs1-11在视神经胶质细胞中均有表达，但在总体水平和亚细胞定位上存在时间差异。HDAC1和2在视神经发育和神经胶质细胞成熟过程中以核为主。HDAC3、5、6、8和11以胞浆为主，但至少在视神经发育的一个阶段显示出核的定位。HDAC4、9和10主要是胞质，在所研究的发育阶段的任何时候都很少或没有核表达。我们的结果表明，在视神经发育和成熟的某些阶段，HDAC 1、2、3、5、6、8和11分别定位于SOX2阳性神经胶质细胞的胞核，推广了先前关于HDAC在老化视神经中表达的报道。这些HDAC是进一步研究的候选细胞，以了解通过乙酰化、脱乙酰化和甲基化而进行的染色质重塑如何促进胶质细胞的发育及其损伤反应。
Histone deacetylases (HDACs) play important roles in glial cell development and in disease states within multiple regions of the central nervous system. However, little is known about HDAC expression or function within the optic nerve. As a first step in understanding the role of HDACs in optic nerve, this study examines the spatio-temporal expression patterns of methylated histone 3 (K9), acetylated histone 3 (K18), and HDACs 1–6 and 8–11 in the developing murine optic nerve head. Using RT-qPCR, western blot and immunofluorescence, three stages were analyzed: embryonic day 16 (E16), when astrocyte precursors are found in the optic stalk, postnatal day 5 (P5), when immature astrocytes and oligodendrocytes are found throughout the optic nerve, and P30, when optic nerve astrocytes and oligodendrocytes are mature. Acetylated and methylated histone H3 immunoreactivity was co-localized in the nuclei of most SOX2 positive glia within the optic nerve head and adjacent optic nerve at all developmental stages. HDACs 1–11 were expressed in the optic nerve glial cells at all three stages of optic nerve development in the mouse, but showed temporal differences in overall levels and subcellular localization. HDACs 1 and 2 were predominantly nuclear throughout optic nerve development and glial cell maturation. HDACs 3, 5, 6, 8, and 11 were predominantly cytoplasmic, but showed nuclear localization in at least one stage of optic nerve development. HDACs 4, 9 and10 were predominantly cytoplasmic, with little to no nuclear expression at any time during the developmental stages examined. Our results showing that HDACs 1, 2, 3, 5, 6, 8, and 11 were each localized to the nuclei of SOX2 positive glia at some stages of optic nerve development and maturation and extend previous reports of HDAC expression in the aging optic nerve. These HDACs are candidates for further research to understand how chromatin remodeling through acetylation, deacetylation and methylation contributes to glial development as well as their injury response.