Maki Nobuyasu, Tsonis Panagiotis A, Agata Kiyokazu
Department of Biology and Center for Tissue Regeneration and Engineering at Dayton, University of Dayton, Dayton, OH 45469-2320, USA.
Mol Vis. 2010 Sep 16;16:1893-7.
Reprogramming of pigmented epithelial cells (PECs) is a decisive process in newt lens regeneration. After lens removal PECs in dorsal iris dedifferentiate and revert to stem cell-like cells, and transdifferentiate into lens cells. Our purpose is to know how global histone modifications are regulated in the reprogramming of PECs.
Iris sections were stained using various histone modification-specific antibodies. The intensity of stained signal in nucleus of PECs was measured and changes in histone modification during dedifferentiation were evaluated.
During dedifferentiation of PECs histone modifications related to gene activation were differentially regulated. Although tri-methylated histone H3 lysine 4 (TriMeH3K4) and acetylated histone H4 (AcH4) were increased, acetylated histone H3 lysine 9 (AcH3K9) was decreased during dedifferentiation. Among all gene repression-related modifications analyzed only tri-methylated histone H3 lysine 27 (TriMeH3K27) showed a significant change. Although in the dorsal iris TriMeH3K27 was kept at same levels after lentectomy, in ventral iris it was increased.
Histone modifications are dynamically changed during dedifferentiation of PECs. A coordination of gene activation-related modifications, increasing of TriMeH3K4 and AcH4 and decreasing of AcH3K9, as well as regulation of TriMeH3K27, could be a hallmark of chromatin regulation during newt dedifferentiation.
色素上皮细胞(PECs)的重编程是蝾螈晶状体再生中的一个决定性过程。晶状体摘除后,背侧虹膜中的PECs去分化并逆转为干细胞样细胞,然后转分化为晶状体细胞。我们的目的是了解在PECs重编程过程中整体组蛋白修饰是如何被调控的。
使用各种组蛋白修饰特异性抗体对虹膜切片进行染色。测量PECs细胞核中染色信号的强度,并评估去分化过程中组蛋白修饰的变化。
在PECs去分化过程中,与基因激活相关的组蛋白修饰受到不同程度的调控。虽然去分化过程中组蛋白H3赖氨酸4三甲基化(TriMeH3K4)和组蛋白H4乙酰化(AcH4)增加,但组蛋白H3赖氨酸9乙酰化(AcH3K9)减少。在所有分析的与基因抑制相关的修饰中,只有组蛋白H3赖氨酸27三甲基化(TriMeH3K27)显示出显著变化。虽然晶状体摘除后背侧虹膜中的TriMeH3K27保持在相同水平,但腹侧虹膜中的TriMeH3K27增加。
在PECs去分化过程中组蛋白修饰动态变化。与基因激活相关的修饰的协调,即TriMeH3K4和AcH4增加以及AcH3K9减少,以及TriMeH3K27的调控,可能是蝾螈去分化过程中染色质调控的一个标志。