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生长抑制蛋白2(ING2)在植入前发育过程中发挥着关键作用。

ING2 (inhibitor of growth protein-2) plays a crucial role in preimplantation development.

作者信息

Zhou Lin, Wang Pei, Zhang Juanjuan, Heng Boon Chin, Tong Guo Qing

机构信息

State Key Laboratory of Reproductive Medicine,Department of Reproduction,Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University,Nanjing 210004,PR China.

Sunway University,Department of Biological Sciences,Faculty of Science & Technology,5 Jalan Universiti,Bandar Sunway 47500,Selangor Darul Ehsan,Malaysia.

出版信息

Zygote. 2016 Feb;24(1):89-97. doi: 10.1017/S0967199414000768. Epub 2015 Feb 12.

Abstract

ING2 (inhibitor of growth protein-2) is a member of the ING-gene family and participates in diverse cellular processes involving tumor suppression, DNA repair, cell cycle regulation, and cellular senescence. As a subunit of the Sin3 histone deacetylase complex co-repressor complex, ING2 binds to H3K4me3 to regulate chromatin modification and gene expression. Additionally, ING2 recruits histone methyltransferase (HMT) activity for gene repression, which is independent of the HDAC class I or II pathway. However, the physiological function of ING2 in mouse preimplantation embryo development has not yet been characterized previously. The expression, localization and function of ING2 during preimplantation development were investigated in this study. We showed increasing expression of ING2 within the nucleus from the 4-cell embryo stage onwards; and that down-regulation of ING2 expression by endoribonuclease-prepared small interfering RNA (esiRNA) microinjection results in developmental arrest during the morula to blastocyst transition. Embryonic cells microinjected with ING2-specific esiRNA exhibited decreased blastulation rate compared to the negative control. Further investigation of the underlying mechanism indicated that down-regulation of ING2 significantly increased expression of p21, whilst decreasing expression of HDAC1. These results suggest that ING2 may play a crucial role in the process of preimplantation embryo development through chromatin regulation.

摘要

ING2(生长抑制蛋白2)是ING基因家族的成员,参与多种细胞过程,包括肿瘤抑制、DNA修复、细胞周期调控和细胞衰老。作为Sin3组蛋白去乙酰化酶复合物共抑制复合物的一个亚基,ING2与H3K4me3结合以调节染色质修饰和基因表达。此外,ING2募集组蛋白甲基转移酶(HMT)活性以进行基因抑制,这独立于I类或II类HDAC途径。然而,ING2在小鼠植入前胚胎发育中的生理功能此前尚未得到表征。本研究调查了ING2在植入前发育过程中的表达、定位和功能。我们发现从4细胞胚胎阶段开始,ING2在细胞核内的表达逐渐增加;通过核糖核酸酶制备的小干扰RNA(esiRNA)显微注射下调ING2表达会导致桑椹胚向囊胚转变过程中的发育停滞。与阴性对照相比,显微注射ING2特异性esiRNA的胚胎细胞囊胚形成率降低。对潜在机制的进一步研究表明,ING2的下调显著增加了p21的表达,同时降低了HDAC1的表达。这些结果表明,ING2可能通过染色质调控在植入前胚胎发育过程中发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f199/4697306/7604e7f70446/S0967199414000768_fig1.jpg

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