MICE DEVELOP NORMALLY WITHOUT THE H1(0) LINKER HISTONE
MICE DEVELOP NORMALLY WITHOUT THE H1(0) LINKER HISTONE
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DOI：
10.1073/pnas.92.14.6434
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发表时间：
1995-07-03
影响因子：
11.1
通讯作者：
SKOULTCHI, AI
中科院分区：
文献类型：
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作者：
SIROTKIN, AM;EDELMANN, W;SKOULTCHI, AI
H1组蛋白与核小体核心颗粒之间的连接物DNA结合，促进染色质折叠成30 nm的纤维，小鼠至少含有七种H1的非等位亚型，包括体细胞变异体H1a至H1e，睾丸特异的变异体HIT，以及替换连接物组蛋白H1(0)，H1(0)在许多谱系的终末分化细胞中积累，大约在细胞停止分裂的时候。为了研究H1(0)在发育中的作用，我们在小鼠胚胎干细胞中通过同源重组破坏了单拷贝H1(0)基因。突变纯合子和完全缺乏H1(0)mRNA和蛋白的小鼠正常生长和繁殖，没有表现出解剖或组织学异常。对H1(0)通常处于高水平的组织的检查也没有发现细胞分裂模式的任何异常。来自H1(0)缺陷动物的染色质在其他患病亚型的相对比例或连接子组蛋白和核小体之间的化学计量学上没有显著变化，这表明其他H1组蛋白可以通过占据正常包含H1(0)的位置来弥补H1(0)的缺陷。我们的结果表明，尽管H1(0)具有独特的性质和表达模式，但其功能对于小鼠的正常发育是必不可少的。
H1 histones bind to the linker DNA between nucleosome core particles and facilitate the folding of chromatin into a 30-nm fiber, Mice contain at least seven nonallelic subtypes of H1, including the somatic variants Hla through H1e, the testis-specific variant Hit, and the replacement linker histone H1(0), H1(0) accumulates in terminally differentiating cells from many lineages, at about the time when the cells cease dividing. To investigate the role of H1(0) in development, we have disrupted the single-copy H1(0) gene by homologous recombination in mouse embryonic stem cells. Mice homozygous for the mutation and completely lacking H1(0) mRNA and protein grew and reproduced normally and exhibited no anatomic or histologic abnormalities. Examination of tissues in which H1(0) is normally present at high levels also failed to reveal any abnormality in cell division patterns. Chromatin from H1(0)-deficient animals showed no significant change in the relative proportions of the other ill subtypes or in the stoichiometry between linker histones and nucleosomes, suggesting that the other H1 histones can compensate for the deficiency in H1(0) by occupying sites that normally contain H1(0). Our results indicate that despite the unique properties and expression pattern of H1(0), its function is dispensable for normal mouse development.