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组蛋白 H2A 不足会导致有丝分裂后期染色体桥形成,从而在裂殖酵母的 rDNA 重复序列处造成染色体分离缺陷。

Histone H2A insufficiency causes chromosomal segregation defects due to anaphase chromosome bridge formation at rDNA repeats in fission yeast.

机构信息

Advanced ICT Research Institute Kobe, National Institute of Information and Communications Technology, 588-2 Iwaoka, Iwaoka-cho, Nishi-ku, Kobe, 651-2492, Japan.

Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, 565-0871, Japan.

出版信息

Sci Rep. 2019 May 9;9(1):7159. doi: 10.1038/s41598-019-43633-5.

Abstract

The nucleosome, composed of DNA and a histone core, is the basic structural unit of chromatin. The fission yeast Schizosaccharomyces pombe has two genes of histone H2A, hta1 and hta2; these genes encode two protein species of histone H2A (H2Aα and H2Aβ, respectively), which differ in three amino acid residues, and only hta2 is upregulated during meiosis. However, it is unknown whether S. pombe H2Aα and H2Aβ have functional differences. Therefore, in this study, we examined the possible functional differences between H2Aα and H2Aβ during meiosis in S. pombe. We found that deletion of hta2, but not hta1, causes defects in chromosome segregation and spore formation during meiosis. Meiotic defects in hta2 deletion cells were rescued by expressing additional copies of hta1 or by expressing hta1 from the hta2 promoter. This indicated that the defects were caused by insufficient amounts of histone H2A, and not by the amino acid residue differences between H2Aα and H2Aβ. Microscopic observation attributed the chromosome segregation defects to anaphase bridge formation in a chromosomal region at the repeats of ribosomal RNA genes (rDNA repeats). These results suggest that histone H2A insufficiency affects the chromatin structures of rDNA repeats, leading to chromosome missegregation in S. pombe.

摘要

核小体由 DNA 和组蛋白核心组成,是染色质的基本结构单位。裂殖酵母 Schizosaccharomyces pombe 有两个组蛋白 H2A 基因,hta1 和 hta2;这些基因编码两种组蛋白 H2A(分别为 H2Aα 和 H2Aβ)的蛋白质,它们在三个氨基酸残基上有所不同,只有 hta2 在减数分裂期间上调。然而,目前尚不清楚 S. pombe H2Aα 和 H2Aβ 是否具有功能差异。因此,在这项研究中,我们研究了 S. pombe 减数分裂过程中 H2Aα 和 H2Aβ 之间可能存在的功能差异。我们发现,hta2 的缺失而非 hta1 的缺失导致减数分裂过程中染色体分离和孢子形成缺陷。在 hta2 缺失细胞中表达额外的 hta1 或在 hta2 启动子的控制下表达 hta1 可挽救减数分裂缺陷。这表明缺陷是由组蛋白 H2A 的含量不足引起的,而不是 H2Aα 和 H2Aβ 之间的氨基酸残基差异引起的。显微镜观察将染色体分离缺陷归因于核糖体 RNA 基因(rDNA 重复)重复区染色体的后期桥形成。这些结果表明,组蛋白 H2A 不足会影响 rDNA 重复的染色质结构,导致 S. pombe 中的染色体错误分离。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4145/6509349/d8e26010d269/41598_2019_43633_Fig1_HTML.jpg

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