Menegola Elena, Cappelletti Graziella, Di Renzo Francesca
Department of Biology, Università degli Studi di Milano, Milan, Italy.
Methods Mol Biol. 2012;889:373-83. doi: 10.1007/978-1-61779-867-2_23.
The relevance of histone acetylation/deacetylation in regulating decompaction/compaction of chromatin and, consequently, in regulating gene expression, has been described for many physiological and pathological biological processes, including normal and altered embryo development. Similarly to other biological systems, also in embryo cells the acetylation status is controlled by the antagonist activity of histone acetyl transferases (HATs) and histone deacetylases (HDACs) and is influenced by other factors acting on chromatin structure (i.e., every epigenetic modification of chromatin). The relevance of acetylation during development has been demonstrated in all developmental phases, from gametogenesis to zygote formation and during early and late embryonic stages. Moreover, the increase number of xenobiotic showing HDAC inhibitory activity recently focused the attention of teratologists on the possible role of HDAC inhibition as a novel teratogenic mechanism. This hypothesis has been demonstrated at least in embryos at somitogenic stages (for mouse embryos from stage E8 till stage E15): HDAC inhibition, histone hyperacetylation, increased cell death (apoptosis) has been suggested as the main event cascade involved in axial skeletal defects induced in rodent by a number of HDAC inhibitors, including the antiepileptic drug valproic acid.
组蛋白乙酰化/去乙酰化在调节染色质解压缩/压缩进而调节基因表达方面的相关性，已在许多生理和病理生物学过程中得到描述，包括正常和异常的胚胎发育。与其他生物系统类似，在胚胎细胞中，乙酰化状态也由组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）的拮抗活性控制，并受作用于染色质结构的其他因素（即染色质的每一种表观遗传修饰）影响。从配子发生到受精卵形成以及胚胎早期和晚期阶段，乙酰化在发育过程中的相关性已在所有发育阶段得到证实。此外，最近显示出HDAC抑制活性的外源性物质数量增加，使致畸学家将注意力集中在HDAC抑制作为一种新型致畸机制的可能作用上。这一假设至少在体节形成阶段的胚胎中得到了证实（对于小鼠胚胎，从E8期到E15期）：HDAC抑制、组蛋白高度乙酰化、细胞死亡增加（凋亡）被认为是多种HDAC抑制剂（包括抗癫痫药物丙戊酸）在啮齿动物中诱导轴向骨骼缺陷所涉及的主要事件级联反应。
