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人类β-珠蛋白基因簇中一种发育稳定的染色质结构。

A developmentally stable chromatin structure in the human beta-globin gene cluster.

作者信息

Forrester W C, Thompson C, Elder J T, Groudine M

出版信息

Proc Natl Acad Sci U S A. 1986 Mar;83(5):1359-63. doi: 10.1073/pnas.83.5.1359.

DOI:10.1073/pnas.83.5.1359
PMID:3456593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC323075/
Abstract

The DNase I-hypersensitive sites in the human embryonic beta-globin gene region have been mapped in erythroid-enriched fractions of disaggregated fetal livers, in adult nucleated red blood cells, and in fetal brain tissue. Our analysis of a region extending 11 kilobases (kb) 5' of the epsilon-globin gene reveals many minor nuclease-hypersensitive sites and one major site located 6.1 kb upstream of the epsilon-globin gene. All of these hypersensitive sites are erythroid-specific, and the major site is stable throughout erythroid development. As assayed by nuclear runoff transcription, little or no epsilon-globin gene expression is detectable in fetal or adult erythroid cells. Thus, the presence of the major hypersensitive site 5' of the epsilon-globin gene in both fetal and adult erythroid cells demonstrates that this site is not specifically correlated with transcription of the gene or with a particular stage of development. Rather, this site may reflect an early event in erythroid differentiation. In addition, DNase I has been used to probe the overall sensitivity of epsilon-globin chromatin in fetal erythroid cells. Our findings indicate that the epsilon-globin gene as well as the other genes in the beta-globin cluster reside within the chromatin domain that is more DNase I-sensitive than "bulk" chromatin.

摘要

人类胚胎β-珠蛋白基因区域中的脱氧核糖核酸酶I超敏位点已在解离的胎儿肝脏富含红细胞的组分、成体有核红细胞以及胎儿脑组织中进行了定位。我们对ε-珠蛋白基因5'端延伸11千碱基(kb)的区域进行分析,发现了许多微小的核酸酶超敏位点以及一个位于ε-珠蛋白基因上游6.1 kb处的主要位点。所有这些超敏位点都是红细胞特异性的,并且该主要位点在整个红细胞发育过程中都是稳定的。通过核转录分析,在胎儿或成体红细胞中几乎检测不到ε-珠蛋白基因的表达。因此,在胎儿和成体红细胞中ε-珠蛋白基因5'端存在主要超敏位点表明,该位点与基因转录或特定发育阶段没有特异性关联。相反,该位点可能反映了红细胞分化中的早期事件。此外,脱氧核糖核酸酶I已被用于探测胎儿红细胞中ε-珠蛋白染色质的整体敏感性。我们的研究结果表明,ε-珠蛋白基因以及β-珠蛋白基因簇中的其他基因位于比“整体”染色质对脱氧核糖核酸酶I更敏感的染色质结构域内。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/f04866047022/pnas00309-0201-h.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/f04866047022/pnas00309-0201-h.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/15ee1eb3ad07/pnas00309-0199-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/c4f9b09de239/pnas00309-0200-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/160adb333a7f/pnas00309-0200-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/2ca7fd1ba041/pnas00309-0200-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/075b80e2a936/pnas00309-0200-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/8400f6366b69/pnas00309-0201-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/95a220ffc0ce/pnas00309-0201-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/fa17df4a4633/pnas00309-0201-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/b8632f4aec74/pnas00309-0201-d.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1e9/323075/f04866047022/pnas00309-0201-h.jpg

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