DNA methylation and transcriptional noise.
DNA methylation and transcriptional noise.
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DOI：
10.1186/1756-8935-6-9
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发表时间：
2013-04-26
影响因子：
3.9
通讯作者：
Yi SV
中科院分区：
文献类型：
--
作者：
Huh I;Zeng J;Park T;Yi SV
DNA甲基化是基因组DNA最广泛的表观遗传学修饰之一。特别是，转录单位(‘基因体’)的DNA甲基化在不同的类群中高度保守。然而，目前对基因体甲基化的功能作用还没有完全了解。一个长期存在的假说认为，基因体甲基化减少了与基因虚假转录相关的转录噪音。尽管这一假设是可信的，但直到现在还没有对这一假设进行明确的检验。利用基因组DNA甲基化的核苷酸分辨数据和丰富的微阵列数据，我们研究了DNA甲基化和转录噪声之间的关系。从微阵列测量的转录噪声随着表达丰度的减少而减少，证实了单细胞研究的结果。我们发现，在其他生物因素的背景下，基因体甲基化与转录噪音显著负相关。这一发现支持了基因体甲基化抑制转录噪音的假设。脊椎动物基因组的高度甲基化可能已经演变为一种控制转录噪音的全球调控机制。相反，启动子甲基化与转录噪声水平呈正相关。我们假设甲基化启动子往往比那些避免DNA甲基化的启动子经历更频繁的转录爆发。
DNA methylation is one of the most phylogenetically widespread epigenetic modifications of genomic DNA. In particular, DNA methylation of transcription units (‘gene bodies’) is highly conserved across diverse taxa. However, the functional role of gene body methylation is not yet fully understood. A long-standing hypothesis posits that gene body methylation reduces transcriptional noise associated with spurious transcription of genes. Despite the plausibility of this hypothesis, an explicit test of this hypothesis has not been performed until now. Using nucleotide-resolution data on genomic DNA methylation and abundant microarray data, here we investigate the relationship between DNA methylation and transcriptional noise. Transcriptional noise measured from microarrays scales down with expression abundance, confirming findings from single-cell studies. We show that gene body methylation is significantly negatively associated with transcriptional noise when examined in the context of other biological factors. This finding supports the hypothesis that gene body methylation suppresses transcriptional noise. Heavy methylation of vertebrate genomes may have evolved as a global regulatory mechanism to control for transcriptional noise. In contrast, promoter methylation exhibits positive correlations with the level of transcriptional noise. We hypothesize that methylated promoters tend to undergo more frequent transcriptional bursts than those that avoid DNA methylation.
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影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
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GEHRKE, C
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通讯作者：
Chess, Andrew