Wellcome Trust/Cancer Research UK Gurdon Institute, Department of Zoology, University of Cambridge, Cambridge, UK.
N Biotechnol. 2011 Jul;28(4):334-41. doi: 10.1016/j.nbt.2010.10.010. Epub 2010 Nov 5.
EMSY interacts directly with BRCA2 and links the BRCA2 pathway to sporadic breast and ovarian cancer. It also interacts with BS69 and HP1b, both of which are involved in chromatin remodelling, and with NIF-1 and DBC-1 in the regulation of nuclear receptor-mediated transcription. Here we investigate the function of EMSY during amphibian development, and in doing so provide the first loss-of-function analysis of this protein. Injection of Xenopus tropicalis embryos with antisense morpholino oligonucleotides targeting XtEMSY impairs gastrulation movements, disrupts dorsal structures, and kills embryos by tailbud stages. Consistent with these observations, regional markers such as Xbra, Chd, Gsc, Shh, Sox3 and Sox17 are downregulated. In contrast to these regional markers, expression of p53 is upregulated in such embryos, and at later stages Bax expression is elevated and apoptotic cells can be detected. Our results demonstrate that EMSY has an essential role in development and they provide an in vivo loss-of-function model that might be used to explore the biochemical functions of this protein in more detail.
EMSY 直接与 BRCA2 相互作用，并将 BRCA2 途径与散发性乳腺癌和卵巢癌联系起来。它还与 BS69 和 HP1b 相互作用，这两者都参与染色质重塑，并且与 NIF-1 和 DBC-1 一起调节核受体介导的转录。在这里，我们研究了 EMSY 在两栖动物发育过程中的功能，从而首次对该蛋白进行了功能丧失分析。针对 XtEMSY 的 Xenopus tropicalis 胚胎注射反义 morpholino 寡核苷酸会损害原肠胚运动，破坏背侧结构，并在尾部芽阶段杀死胚胎。与这些观察结果一致，区域标记物（如 Xbra、Chd、Gsc、Shh、Sox3 和 Sox17）的表达下调。与这些区域标记物相反，p53 在这些胚胎中的表达上调，并且在后期阶段 Bax 的表达升高并且可以检测到凋亡细胞。我们的结果表明，EMSY 在发育中具有重要作用，并且它们提供了一种体内功能丧失模型，可用于更详细地探索该蛋白的生化功能。
