Astrocyte-specific genes are generally demethylated in neural precursor cells prior to astrocytic differentiation.
Astrocyte-specific genes are generally demethylated in neural precursor cells prior to astrocytic differentiation.
复制标题
DOI：
10.1371/journal.pone.0003189
复制
发表时间：
2008-09-11
期刊：
影响因子：
3.7
通讯作者：
Nakashima K
中科院分区：
文献类型：
--
作者：
Hatada I;Namihira M;Morita S;Kimura M;Horii T;Nakashima K
表观遗传变化被认为会导致细胞特性的改变，如分化潜能。神经前体细胞（NPC）仅在妊娠中期的大脑中分化为神经元，但它们在发育后期能够产生星形胶质细胞。这种分化潜能转换可以通过表观遗传学变化来解释，因为星形胶质细胞特异性标记基因的启动子，胶质细胞酸性蛋白（GFAP）和S100β，已经被证明在星形胶质细胞分化开始之前在晚期NPC中变得去甲基化;然而，去甲基化是否普遍发生在其他星形胶质细胞基因中仍然未知。在这里，我们分析了DNA甲基化的变化，在小鼠NPC之间的中期（E11.5）和晚期（E14.5）的发展阶段，通过全基因组DNA甲基化分析方法，使用微阵列，发现许多星形胶质细胞基因在晚期NPC中去甲基化，使细胞能够表达这些基因。虽然这些基因在晚期NPC中已经去甲基化，但它们直到细胞分化成星形胶质细胞才表达。因此，晚期NPC具有表观遗传潜力，其可以在星形胶质细胞分化后的表达中实现。
Epigenetic changes are thought to lead to alterations in the property of cells, such as differentiation potential. Neural precursor cells (NPCs) differentiate only into neurons in the midgestational brain, yet they become able to generate astrocytes in the late stage of development. This differentiation-potential switch could be explained by epigenetic changes, since the promoters of astrocyte-specific marker genes, glial fibrillary acidic protein (Gfap) and S100β, have been shown to become demethylated in late-stage NPCs prior to the onset of astrocyte differentiation; however, whether demethylation occurs generally in other astrocyctic genes remains unknown. Here we analyzed DNA methylation changes in mouse NPCs between the mid-(E11.5) and late (E14.5) stage of development by a genome-wide DNA methylation profiling method using microarrays and found that many astrocytic genes are demethylated in late-stage NPCs, enabling the cell to become competent to express these genes. Although these genes are already demethylated in late-stage NPCs, they are not expressed until cells differentiate into astrocytes. Thus, late-stage NPCs have epigenetic potential which can be realized in their expression after astrocyte differentiation.
登录
查看更多内容
影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
影响因子：
64.5
作者：
Czermin, B;Melfi, R;Pirrotta, V
通讯作者：
Pirrotta, V
影响因子：
56.9
作者：
Bonni, A;Sun, Y;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
3.5
作者：
Namihira, M;Nakashima, K;Taga, T
通讯作者：
Taga, T
影响因子：
2.5
作者：
Neusch, C;Papadopoulos, N;Hülsmann, S
通讯作者：
Hülsmann, S