Stadler Jochen A, Shkumatava Alena, Norton William H J, Rau Marlene J, Geisler Robert, Fischer Sabine, Neumann Carl J
European Molecular Biology Laboratory, Heidelberg, Germany.
Dev Dyn. 2005 Jul;233(3):883-9. doi: 10.1002/dvdy.20427.
Histone acetylation is an important epigenetic mechanism for the control of eukaryotic transcription. The histone deacetylase 1 (HDAC1) gene has been implicated in controlling the transcription of core cell cycle regulators, but the in vivo role of HDACs in cell cycle regulation is still poorly understood. Loss of HDAC1 activity causes underproliferation in several contexts during vertebrate development. In contrast, we show here that HDAC1 has the opposite effect in the zebrafish visual system, where loss of HDAC1 activity leads to failure of cells to exit the cell cycle in the retina and in the optic stalk. The effect of HDAC1 on cell cycle exit is cell-autonomous, and loss of HDAC1 in the retina leads to up-regulation of cyclin D and E transcripts. These results demonstrate that the in vivo role of HDAC1 in regulating cell cycle progression is region-specific, as HDAC1 promotes cell cycle exit in the retina but stimulates proliferation in other cellular contexts.
组蛋白乙酰化是控制真核生物转录的一种重要表观遗传机制。组蛋白去乙酰化酶1（HDAC1）基因与核心细胞周期调节因子的转录控制有关，但HDACs在细胞周期调控中的体内作用仍知之甚少。在脊椎动物发育过程中的多种情况下，HDAC1活性丧失会导致细胞增殖不足。相比之下，我们在此表明HDAC1在斑马鱼视觉系统中具有相反的作用，在该系统中，HDAC1活性丧失会导致视网膜和视柄中的细胞无法退出细胞周期。HDAC1对细胞周期退出的影响是细胞自主性的，视网膜中HDAC1的缺失会导致细胞周期蛋白D和E转录本上调。这些结果表明，HDAC1在调节细胞周期进程中的体内作用具有区域特异性，因为HDAC1促进视网膜中的细胞周期退出，但在其他细胞环境中刺激细胞增殖。
