Ribosomal DNA deletions modulate genome-wide gene expression: "rDNA-sensitive" genes and natural variation.
Ribosomal DNA deletions modulate genome-wide gene expression: "rDNA-sensitive" genes and natural variation.
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DOI：
10.1371/journal.pgen.1001376
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发表时间：
2011-04
期刊：
影响因子：
4.5
通讯作者：
Lemos B
中科院分区：
文献类型：
--
作者：
Paredes S;Branco AT;Hartl DL;Maggert KA;Lemos B
核糖体rDNA基因阵列是一种表观遗传调控的重复基因位点。虽然rDNA拷贝数在物种之间和物种内部差异很大，但微妙拷贝数多态性的功能后果在很大程度上是未知的。果蝇y链rDNA的缺失修饰了异染色质诱导的位置效应变异（PEV），但目前尚不清楚基因组的常染色质成分是否受到rDNA拷贝数的影响。自然发生的Y染色体多态性影响常染色质和异染色质，尽管负责这些影响的因素尚不清楚。在这里，我们表明y链rDNA阵列的拷贝数是基因表达全基因组变异的一个来源。rDNA的诱导缺失会影响整个雄性和雌性基因组中数百到数千个常染色基因的表达。虽然受影响的基因没有物理聚集，但我们观察到其蛋白质产物位于线粒体并参与电子传递的基因的功能富集。受影响的基因与Y染色体上受自然多态性影响的基因显著重叠，表明多态性rDNA拷贝数是自然群体中基因表达多样性的重要决定因素。总之，我们的研究结果表明，个体之间rDNA拷贝数的细微变化可能有助于生物学上相关的表型变异。重复的rDNA阵列产生了核仁，核仁是最早被描述的细胞内结构之一，已知参与关键的细胞过程，如应激反应、细胞周期调节、RNA修饰和90%以上的细胞RNA（核糖体RNA）的产生。rDNA过量存在；而且，尽管许多拷贝通过表观遗传机制失活，但失活拷贝的生物学意义一直存在争议。我们提出了一个系统，该系统允许识别由rDNA拷贝数差异引起的全球基因表达效应。我们已经发现，rDNA位点的缺失导致数百到数千个基因的差异表达。这提出了一种期望，即影响健康和疾病的重要表型变异可能追溯到rDNA拷贝数的多态性变异。此外，rDNA拷贝数的多重效应表明，考虑rDNA的多态性可能会为表观遗传研究及其对复杂性状遗传力的贡献带来新的思路。
The ribosomal rDNA gene array is an epigenetically-regulated repeated gene locus. While rDNA copy number varies widely between and within species, the functional consequences of subtle copy number polymorphisms have been largely unknown. Deletions in the Drosophila Y-linked rDNA modifies heterochromatin-induced position effect variegation (PEV), but it has been unknown if the euchromatic component of the genome is affected by rDNA copy number. Polymorphisms of naturally occurring Y chromosomes affect both euchromatin and heterochromatin, although the elements responsible for these effects are unknown. Here we show that copy number of the Y-linked rDNA array is a source of genome-wide variation in gene expression. Induced deletions in the rDNA affect the expression of hundreds to thousands of euchromatic genes throughout the genome of males and females. Although the affected genes are not physically clustered, we observed functional enrichments for genes whose protein products are located in the mitochondria and are involved in electron transport. The affected genes significantly overlap with genes affected by natural polymorphisms on Y chromosomes, suggesting that polymorphic rDNA copy number is an important determinant of gene expression diversity in natural populations. Altogether, our results indicate that subtle changes to rDNA copy number between individuals may contribute to biologically relevant phenotypic variation. The repeated rDNA array gives rise to the nucleolus, which is one of the first described intracellular structures and is known to be involved in key cellular processes such as stress response, cell cycle regulation, RNA modification, and production of more than 90% of all cellular RNAs (the ribosomal RNAs). The rDNA exists in excess; and, although many copies are inactivated through epigenetic mechanisms, the biological significance of inactive copies has been a matter of debate. We present a system that allows for the identification of global gene expression effects stemming from differences in rDNA copy number. We have discovered that deletions in the rDNA locus result in the differential expression of hundreds to thousands of genes. This raises the expectation that important phenotypic variation affecting health and disease might be traced to polymorphic variation in rDNA copy number. Furthermore, the manifold effects of rDNA copy number indicate that considering polymorphisms in the rDNA might bring new light to studies of epigenetic inheritance and its contribution to the heritability of complex traits.
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影响因子：
7
作者：
Cohen, S;Yacobi, K;Segal, D
通讯作者：
Segal, D
DOI：
10.1073/pnas.0906811106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Paredes, Silvana;Maggert, Keith A.
通讯作者：
Maggert, Keith A.
影响因子：
64.5
作者：
Ahmad, K;Henikoff, S
通讯作者：
Henikoff, S
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.2
作者：
Cullis, CA
通讯作者：
Cullis, CA