H1 linker histories are essential for mouse development and affect nucleosome spacing in vivo
H1 linker histories are essential for mouse development and affect nucleosome spacing in vivo
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DOI：
10.1128/mcb.23.13.4559-4572.2003
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发表时间：
2003-07-01
影响因子：
5.3
通讯作者：
Skoultchi, AI
中科院分区：
文献类型：
--
作者：
Fan, YH;Nikitina, T;Skoultchi, AI
大多数真核细胞含有几乎等摩尔量的核小体和H1接头组蛋白。尽管它们的丰度和潜在的功能专业化的H1亚型在多细胞生物体中，基因失活的研究未能揭示接头组蛋白在体内的基本功能。此外，体外研究表明，H1亚型可能不是染色体或细胞核组装所必需的。通过顺序灭活三种小鼠H1亚型（H1c，H1d和H1e）的基因，我们发现连接组蛋白对哺乳动物发育至关重要。缺乏三种HI亚型的胚胎在妊娠中期死亡，并伴有广泛的缺陷。三重H1缺失胚胎的H1与核小体的比例约为正常的50%。这六个H1等位基因中有五个缺失的小鼠是可以存活的，但在窝仔中代表性不足，并且比它们的窝仔小得多。在这些小鼠的某些组织和另一种化合物H1突变体中发现H1含量显著降低。这些结果表明，H1的总量对胚胎的正常发育至关重要。在某些组织中，H1的大量减少并不导致核大小的变化，但它确实导致核小体之间的间距的整体缩短。
Most eukaryotic cells contain nearly equimolar amounts of nucleosomes and H1 linker histones. Despite their abundance and the potential functional specialization of H1 subtypes in multicellular organisms, gene inactivation studies have failed to reveal essential functions for linker histones in vivo. Moreover, in vitro studies suggest that H1 subtypes may not be absolutely required for assembly of chromosomes or nuclei. By sequentially inactivating the genes for three mouse H1 subtypes (H1c, H1d, and H1e), we showed that linker histones are essential for mammalian development. Embryos lacking the three HI subtypes die by mid-gestation with a broad range of defects. Triple-H1-null embryos have about 50% of the normal ratio of H1 to nucleosomes. Mice null for five of these six H1 alleles are viable but are underrepresented in litters and are much smaller than their littermates. Marked reductions in H1 content were found in certain tissues of these mice and in another compound H1 mutant. These results demonstrate that the total amount of H1 is crucial for proper embryonic development. Extensive reduction of H1 in certain tissues did not lead to changes in nuclear size, but it did result in global shortening of the spacing between nucleosomes.