Laboratory of Cell Morphology, Institute of Cytology of the Russian Academy of Sciences, 4 Tikhoretsky Ave., 194064 St. Petersburg, Russia.
Int J Mol Sci. 2021 Jan 28;22(3):1313. doi: 10.3390/ijms22031313.
The Death-domain associated protein 6 (DAXX) is an evolutionarily conserved and ubiquitously expressed multifunctional protein that is implicated in many cellular processes, including transcription, cellular proliferation, cell cycle regulation, Fas-induced apoptosis, and many other events. In the nucleus, DAXX interacts with transcription factors, epigenetic modifiers, and chromatin-remodeling proteins such as the transcription regulator ATRX-the α-thalassemia/mental retardation syndrome X-linked ATP-dependent helicase II. Accordingly, DAXX is considered one of the main players involved in chromatin silencing and one of the most important factors that maintain integrity of the genome. In this brief review, we summarize available data regarding the general and specific functions of DAXX in mammalian early development, with special emphasis on the function of DAXX as a chaperone of the histone variant H3.3. Since H3.3 plays a key role in the developmental processes, especially in the pronounced rearrangements of heterochromatin compartment during oogenesis and embryogenesis, DAXX can be considered as an important factor supporting proper development. Specifically, loss of DAXX affects the recruitment of ATRX, transcription of tandem repeats and telomere functions, which results in a decrease in the viability of early embryos.
死亡结构域相关蛋白 6（DAXX）是一种进化上保守且广泛表达的多功能蛋白，参与多种细胞过程，包括转录、细胞增殖、细胞周期调控、Fas 诱导的细胞凋亡以及许多其他事件。在细胞核内，DAXX 与转录因子、表观遗传修饰因子以及染色质重塑蛋白相互作用，如转录调节因子 ATRX-α-地中海贫血/智力迟钝综合征 X 连锁 ATP 依赖性解旋酶 II。因此，DAXX 被认为是参与染色质沉默的主要参与者之一，也是维持基因组完整性的最重要因素之一。在这篇简短的综述中，我们总结了有关 DAXX 在哺乳动物早期发育中的一般和特定功能的现有数据，特别强调了 DAXX 作为组蛋白变体 H3.3 伴侣的功能。由于 H3.3 在发育过程中起着关键作用，尤其是在卵母细胞发生和胚胎发生过程中异染色质区室的明显重排，因此 DAXX 可以被认为是支持正常发育的重要因素。具体而言，DAXX 的缺失会影响 ATRX 的募集、串联重复序列的转录和端粒功能，从而导致早期胚胎的活力下降。
