Lilja Tobias, Heldring Nina, Hermanson Ola
Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE17177 Stockholm, Sweden.
Biochim Biophys Acta. 2013 Feb;1830(2):2354-60. doi: 10.1016/j.bbagen.2012.08.011. Epub 2012 Aug 16.
The development of the nervous system is a highly organized process involving the precise and coordinated timing of many complex events. These events require proper expression of genes promoting survival, differentiation, and maturation, but also repression of alternative cell fates and restriction of cell-type-specific gene expression.
As the enzymes mediating post-translational histone acetylation and methylation are regulating higher order chromatin structure and controlling gene transcription, knowledge of the roles for these enzymes becomes crucial for understanding neural development and disease. The widespread expression and general biological roles for chromatin-modifying factors have hampered the studies of such enzymes in neural development, but in recent years, in vivo and in vitro studies have started to shed light on the various processes these enzymes regulate. In this review we summarize the implications of chromatin-modifying enzymes in neural development, with particular emphasis on enzymes regulating histone acetylation and methylation.
Enzymes controlling histone acetylation and methylation are involved in the whole process of neural development, from controlling proliferation and undifferentiated, "poised", state of stem cells to promoting and inhibiting neurogenic and gliogenic pathways and neuronal survival as well as neurite outgrowth.
Aberrant enzymatic activities of histone acetyl transferases, deacetylases, and demethylases have been chemically and genetically associated with neural developmental disorders and cancer. Future studies may aim at linking the genetic and developmental studies to more in-depth biochemical characterization to provide a clearer picture of how to improve the diagnosis, prognosis, and treatment of such disorders. This article is part of a Special Issue entitled Biochemistry of Stem Cells.
神经系统的发育是一个高度有序的过程，涉及许多复杂事件的精确和协调的时间安排。这些事件不仅需要促进存活、分化和成熟的基因的正确表达，还需要抑制替代细胞命运以及限制细胞类型特异性基因表达。
由于介导翻译后组蛋白乙酰化和甲基化的酶调节高级染色质结构并控制基因转录，了解这些酶的作用对于理解神经发育和疾病至关重要。染色质修饰因子的广泛表达和一般生物学作用阻碍了对这些酶在神经发育中的研究，但近年来，体内和体外研究已开始揭示这些酶调节的各种过程。在本综述中，我们总结了染色质修饰酶在神经发育中的意义，特别强调调节组蛋白乙酰化和甲基化的酶。
控制组蛋白乙酰化和甲基化的酶参与神经发育的全过程，从控制干细胞的增殖和未分化的“ poised ”状态到促进和抑制神经发生和胶质发生途径以及神经元存活以及神经突生长。
组蛋白乙酰转移酶、去乙酰化酶和去甲基化酶的异常酶活性在化学和遗传上与神经发育障碍和癌症相关。未来的研究可能旨在将遗传和发育研究与更深入的生化特征联系起来，以更清楚地了解如何改善此类疾病的诊断、预后和治疗。本文是名为“干细胞生物化学”的特刊的一部分。
