Arakawa Tatsuhiko, Nakatani Tsunetoshi, Oda Masaaki, Kimura Yasuyoshi, Sekita Yoichi, Kimura Tohru, Nakamura Toshinobu, Nakano Toru
Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
Department of Pathology, Osaka University, Osaka 565-0871, Japan; Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Saitama 332-0012, Japan.
Biochem Biophys Res Commun. 2015 Oct 9;466(1):60-5. doi: 10.1016/j.bbrc.2015.08.106. Epub 2015 Aug 29.
In mammals, the structure of the pericentromeric region alters from a ring structure to a dot-like structure during the 2-cell stage. This structural alteration is termed chromocenter formation (CF) and is required for preimplantation development. Although reverse transcripts of major satellite repeats at pericentromeric regions are known to play roles in CF, its underlying mechanism is not fully understood. We previously reported that Stella (also known as PGC7 and Dppa3) deficiency led to developmental arrest at the preimplantation stage, accompanied by frequent chromosome segregation. In this study, we further investigated the effect of Stella deficiency on chromatin reorganization. The Stella-null embryos exhibited impaired CF and reduced expression of the reverse strand of major satellite repeats. In addition, the accumulation of H3.3, a histone H3 variant associated with transcriptional activation, at the pericentromeric regions and expression of the H3.3-specific chaperone Daxx were reduced in Stella-null embryos. These abnormalities were restored by the enforced expression of Daxx in Stella-null embryos. Thus, Stella controls the expression of Daxx and ensures chromatin reorganization in early embryos.
在哺乳动物中，着丝粒周围区域的结构在二细胞期从环状结构转变为点状结构。这种结构改变被称为染色中心形成（CF），是着床前发育所必需的。虽然已知着丝粒周围区域主要卫星重复序列的逆转录产物在CF中发挥作用，但其潜在机制尚未完全了解。我们之前报道过，Stella（也称为PGC7和Dppa3）缺陷导致着床前阶段发育停滞，并伴有频繁的染色体分离。在本研究中，我们进一步研究了Stella缺陷对染色质重组的影响。缺乏Stella的胚胎表现出CF受损以及主要卫星重复序列反义链的表达降低。此外，与转录激活相关的组蛋白H3变体H3.3在着丝粒周围区域的积累以及H3.3特异性伴侣蛋白Daxx的表达在缺乏Stella的胚胎中减少。在缺乏Stella的胚胎中强制表达Daxx可恢复这些异常。因此，Stella控制Daxx的表达并确保早期胚胎中的染色质重组。
