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受精或体细胞核移植后H1连接组蛋白的快速转变:小鼠中统一发育程序的证据

Rapid H1 linker histone transitions following fertilization or somatic cell nuclear transfer: evidence for a uniform developmental program in mice.

作者信息

Gao Shaorong, Chung Young Gie, Parseghian Missag H, King Gretchen J, Adashi Eli Y, Latham Keith E

机构信息

Department of Biochemistry, The Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.

出版信息

Dev Biol. 2004 Feb 1;266(1):62-75. doi: 10.1016/j.ydbio.2003.10.003.

DOI:10.1016/j.ydbio.2003.10.003
PMID:14729478
Abstract

H1 linker histones (H1s) are key regulators of chromatin structure and function. The functions of different H1s during early embryogenesis, and mechanisms regulating their associations with chromatin are largely unknown. The developmental transitions of H1s during oocyte growth and maturation, fertilization and early embryogenesis, and in cloned embryos were examined. Oocyte-specific H1FOO, but not somatic H1s, associated with chromatin in oocytes (growing, GV-stage, and MII-arrested), pronuclei, and polar bodies. H1FOO associated with sperm or somatic cell chromatin within 5 min of intracytoplasmic sperm injection (ICSI) or somatic cell nuclear transfer (SCNT), and completely replaced somatic H1s by 60 min. The switching from somatic H1s to H1FOO following SCNT was developmentally regulated. H1FOO was replaced by somatic H1s during the late two- and four-cell stages. H1FOO association with chromatin can occur in the presence of a nuclear envelope and independently of pronucleus formation, is regulated by factors associated with the spindle, and is likely an active process. All SCNT constructs recapitulated the normal sequence of H1 transitions, indicating that this alone does not signify a high developmental potential. A paucity of all known H1s in two-cell embryos may contribute to precocious gene transcription in fertilized embryos, and the elaboration of somatic cell characteristics in cloned embryos.

摘要

H1连接组蛋白(H1s)是染色质结构和功能的关键调节因子。不同H1s在早期胚胎发育过程中的功能以及调节它们与染色质结合的机制在很大程度上尚不清楚。研究了H1s在卵母细胞生长和成熟、受精和早期胚胎发育以及克隆胚胎中的发育转变。卵母细胞特异性H1FOO而非体细胞H1s与卵母细胞(生长中的、GV期和MII期阻滞的)、原核和极体中的染色质结合。在胞浆内精子注射(ICSI)或体细胞核移植(SCNT)后5分钟内,H1FOO与精子或体细胞染色质结合,并在60分钟内完全取代体细胞H1s。SCNT后从体细胞H1s向H1FOO的转换受发育调控。在二细胞期和四细胞期后期,H1FOO被体细胞H1s取代。H1FOO与染色质的结合可在有核膜存在的情况下发生,且独立于原核形成,受与纺锤体相关的因子调控,并且可能是一个主动过程。所有SCNT构建体都重现了H1转换的正常顺序,表明仅此一点并不意味着具有高发育潜力。二细胞胚胎中所有已知H1s的缺乏可能导致受精胚胎中基因转录早熟,以及克隆胚胎中体细胞特征的形成。

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