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逆转录病毒诱导的小鼠I型胶原蛋白基因致死性突变与染色质结构改变有关。

Retrovirus-induced lethal mutation in collagen I gene of mice is associated with an altered chromatin structure.

作者信息

Breindl M, Harbers K, Jaenisch R

出版信息

Cell. 1984 Aug;38(1):9-16. doi: 10.1016/0092-8674(84)90521-x.

DOI:10.1016/0092-8674(84)90521-x
PMID:6088079
Abstract

The chromatin structure of the collagen alpha 1(I) gene, which has been mutated by retrovirus insertion in Mov13 mice, was compared with that of the wildtype allele. Limited digestions with DNAase I revealed the presence of two hypersensitive sites in all normal cells analyzed, while a third site at 100 to 200 bp 5' of the transcription start was detected only in cells synthesizing collagen alpha 1(I) mRNA. This transcription-associated site was not present in chromatin of the mutant allele, while the two other hypersensitive sites, one of which is located close to the provirus, were not changed by the virus integration. Our results suggest that the virus insertion in Mov13 mice may prevent the developmentally regulated appearance of a transcription-associated hypersensitive site, thereby interfering with proper activation of the gene during embryonic development.

摘要

在Mov13小鼠中,因逆转录病毒插入而发生突变的胶原蛋白α1(I)基因的染色质结构,与野生型等位基因的染色质结构进行了比较。用DNA酶I进行有限消化后发现,在所有分析的正常细胞中都存在两个超敏位点,而仅在合成胶原蛋白α1(I)mRNA的细胞中,才检测到位于转录起始位点5'端100至200 bp处的第三个位点。这个与转录相关的位点在突变等位基因的染色质中不存在,而另外两个超敏位点,其中一个靠近前病毒,并未因病毒整合而改变。我们的结果表明,Mov13小鼠中的病毒插入可能会阻止与转录相关的超敏位点在发育过程中的出现,从而干扰胚胎发育过程中该基因的正常激活。

相似文献

1
Retrovirus-induced lethal mutation in collagen I gene of mice is associated with an altered chromatin structure.逆转录病毒诱导的小鼠I型胶原蛋白基因致死性突变与染色质结构改变有关。
Cell. 1984 Aug;38(1):9-16. doi: 10.1016/0092-8674(84)90521-x.
2
Restriction enzyme digestions identify discrete domains in the chromatin around the promoter of the mouse alpha 2(I) collagen gene.限制性酶切鉴定出小鼠α2(I)胶原基因启动子周围染色质中的离散结构域。
J Biol Chem. 1986 Aug 25;261(24):11362-8.
3
Retrovirus-induced interference with collagen I gene expression in Mov13 fibroblasts is maintained in the absence of DNA methylation.逆转录病毒诱导的对Mov13成纤维细胞中I型胶原基因表达的干扰在不存在DNA甲基化的情况下仍会持续。
Mol Cell Biol. 1991 Jan;11(1):47-54. doi: 10.1128/mcb.11.1.47-54.1991.
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Retrovirus insertion inactivates mouse alpha 1(I) collagen gene by blocking initiation of transcription.逆转录病毒插入通过阻断转录起始使小鼠α1(I)胶原蛋白基因失活。
Nature. 1986;320(6060):365-7. doi: 10.1038/320365a0.
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Retrovirus-induced insertional mutagenesis: mechanism of collagen mutation in Mov13 mice.
Mol Cell Biol. 1991 Oct;11(10):5154-63. doi: 10.1128/mcb.11.10.5154-5163.1991.
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Embryonic lethal mutation in mice induced by retrovirus insertion into the alpha 1(I) collagen gene.逆转录病毒插入α1(I)胶原基因诱导小鼠胚胎致死性突变。
Nature. 1983;304(5924):315-20. doi: 10.1038/304315a0.
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DNase I sensitivity of the alpha 2(I) collagen gene: correlation with its expression but not with its methylation pattern.α2(I)型胶原蛋白基因的脱氧核糖核酸酶I敏感性:与其表达相关,但与其甲基化模式无关。
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Insertion of retrovirus into the first intron of alpha 1(I) collagen gene to embryonic lethal mutation in mice.将逆转录病毒插入小鼠α1(I)胶原基因的第一个内含子导致胚胎致死突变。
Proc Natl Acad Sci U S A. 1984 Mar;81(5):1504-8. doi: 10.1073/pnas.81.5.1504.
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The lethal yellow allele-associated provirus results in the production of chimeric viral-host RNAs.致死性黄色等位基因相关的前病毒导致嵌合病毒-宿主RNA的产生。
Proc Natl Acad Sci U S A. 1987 May;84(9):2853-7. doi: 10.1073/pnas.84.9.2853.
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Retrovirus integration and chromatin structure: Moloney murine leukemia proviral integration sites map near DNase I-hypersensitive sites.逆转录病毒整合与染色质结构:莫洛尼鼠白血病病毒前病毒整合位点定位于DNA酶I超敏位点附近。
J Virol. 1987 Feb;61(2):336-43. doi: 10.1128/JVI.61.2.336-343.1987.

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