气候变化领域集成服务门户(CCPortal): Reduction in gene expression noise by targeted increase in accessibility at gene loci

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DOI	10.1073/pnas.2018640118
	Reduction in gene expression noise by targeted increase in accessibility at gene loci
	Fraser L.C.R.; Dikdan R.J.; Dey S.; Singh A.; Tyagi S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:42
英文摘要	Many eukaryotic genes are expressed in randomly initiated bursts that are punctuated by periods of quiescence. Here, we show that the intermittent access of the promoters to transcription factors through relatively impervious chromatin contributes to this "noisy" transcription. We tethered a nuclease-deficient Cas9 fused to a histone acetyl transferase at the promoters of two endogenous genes in HeLa cells. An assay for transposase-accessible chromatin using sequencing showed that the activity of the histone acetyl transferase altered the chromatin architecture locally without introducing global changes in the nucleus and rendered the targeted promoters constitutively accessible. We measured the gene expression variability from the gene loci by performing single-molecule fluorescence in situ hybridization against mature messenger RNAs (mRNAs) and by imaging nascent mRNA molecules present at active gene loci in single cells. Because of the increased accessibility of the promoter to transcription factors, the transcription from two genes became less noisy, even when the average levels of expression did not change. In addition to providing evidence for chromatin accessibility as a determinant of the noise in gene expression, our study offers a mechanism for controlling gene expression noise which is otherwise unavoidable. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Single-cell heterogeneity; Stochastic mRNA synthesis; Transcriptional bursting
语种	英语
scopus关键词	histone acetyltransferase; messenger RNA; transcription factor; transferase; Article; chromatin; controlled study; fluorescence in situ hybridization; gene expression; gene locus; gene sequence; gene targeting; HeLa cell line; human; human cell; promoter region; RNA synthesis
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238776
作者单位	Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ 07103, United States; Department of Electrical and Computer Engineering, University of Delaware, Newark, DE 19716, United States; Department of Biomedical Engineering, University of Delaware, Newark, DE 19713, United States; Department of Mathematical Sciences, University of Delaware, Newark, DE 19716, United States; Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103, United States
推荐引用方式 GB/T 7714	Fraser L.C.R.,Dikdan R.J.,Dey S.,et al. Reduction in gene expression noise by targeted increase in accessibility at gene loci[J],2021,118(42).
APA	Fraser L.C.R.,Dikdan R.J.,Dey S.,Singh A.,&Tyagi S..(2021).Reduction in gene expression noise by targeted increase in accessibility at gene loci.Proceedings of the National Academy of Sciences of the United States of America,118(42).
MLA	Fraser L.C.R.,et al."Reduction in gene expression noise by targeted increase in accessibility at gene loci".Proceedings of the National Academy of Sciences of the United States of America 118.42(2021).