Kandolf H
Research Institute of Molecular Pathology, Vienna, Austria.
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7257-61. doi: 10.1073/pnas.91.15.7257.
Previous in vitro transcription studies have pointed to the importance of histone H1 for repression of oocyte-type 5S genes of Xenopus laevis. It has been previously reported that in development up to the early gastrula stage, Xenopus embryos contain a large pool of the maternal histone H1 variant H1M but are virtually devoid of histone H1A, H1B, and H1C proteins. At the early gastrula stage, there is an increase in H1A protein synthesis and H1A becomes the predominant H1 histone variant. Concomitant with the significant appearance of H1A protein in chromatin, oocyte 5S transcription is repressed. Here it is shown that there appears to be a direct link between H1A accumulation and inhibition of oocyte-type 5S RNA synthesis. Inhibition of H1A synthesis by a ribozyme targeted to H1A mRNA leads to the continued expression of oocyte 5S genes. H1A is proposed to inhibit major oocyte 5S gene transcription by sealing the nucleosome that is positioned over the major oocyte 5S coding sequences and by driving major oocyte 5S gene chromatin into a higher-order structure in which histone H1A molecules interact cooperatively.
以往的体外转录研究表明，组蛋白H1对非洲爪蟾卵母细胞型5S基因的抑制具有重要作用。此前有报道称，在发育至早期原肠胚阶段之前，非洲爪蟾胚胎含有大量母源组蛋白H1变体H1M，但几乎不含组蛋白H1A、H1B和H1C蛋白。在早期原肠胚阶段，H1A蛋白合成增加，H1A成为主要的H1组蛋白变体。随着H1A蛋白在染色质中的显著出现，卵母细胞5S转录受到抑制。本文表明，H1A积累与卵母细胞型5S RNA合成抑制之间似乎存在直接联系。靶向H1A mRNA的核酶抑制H1A合成会导致卵母细胞5S基因持续表达。有人提出，H1A通过封闭位于主要卵母细胞5S编码序列上的核小体，并将主要卵母细胞5S基因染色质驱动成一种高阶结构，使组蛋白H1A分子协同相互作用，从而抑制主要卵母细胞5S基因转录。
