scholarly journals Quantitative Control of Noise in Mammalian Gene Expression by Dynamic Histone Regulations

2020 ◽  
Author(s):  
Deng Tan ◽  
Rui Chen ◽  
Yuejian Mo ◽  
Wei Xu ◽  
Xibin Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Expression System ◽  
Transcriptional Activator ◽  
Chromatin Accessibility ◽  
Gene Expressions ◽  
Positive Feedback Loop ◽  
Dynamic Regulation ◽  
Endogenous Gene

AbstractFluctuation (‘noise’) in gene expression is critical for mammalian cellular processes. Numerous mechanisms contribute to its origins, yet large noises induced by single transcriptional activator species remain to be experimentally understood. Here, we combined the dynamic regulation of transcriptional activator binding, histone regulator inhibitors, and single-cell quantification of chromatin accessibility, mRNA, and protein to probe putative mechanisms. Using a light-induced expression system, we show that the transcriptional activator forms a positive feedback loop with histone acetyltransferases CBP/p300. It generates epigenetic bistability in H3K27ac, which contributes to large noise. Disable of the positive feedback loop by CBP/p300 and HDAC4/5 inhibitors also reduces heterogeneity in endogenous genes, suggesting a universal mechanism. We showed that the noise was reduced by pulse-wide modulation of transcriptional activator binding due to alternating the system between high and low monostable states. Our findings could provide a mechanism-based approach to modulate noise in synthetic and endogenous gene expressions.

scholarly journals Quantitative control of noise in mammalian gene expression by dynamic histone regulation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Deng Tan ◽  
Rui Chen ◽  
Yuejian Mo ◽  
Shu Gu ◽  
Jiao Ma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cells ◽  
Expression System ◽  
Transcriptional Activator ◽  
Chromatin Accessibility ◽  
Dynamic Regulation ◽  
Endogenous Gene ◽  
Dual Functional ◽  
Fluctuation Noise ◽  
Noise In Gene Expression

Fluctuation ('noise') in gene expression is critical for mammalian cellular processes. Numerous mechanisms contribute to its origins, yet the mechanisms behind large fluctuations that are induced by single transcriptional activators remain elusive. Here, we probed putative mechanisms by studying the dynamic regulation of transcriptional activator binding, histone regulator inhibitors, chromatin accessibility, and levels of mRNAs and proteins in single cells. Using a light-induced expression system, we showed that the transcriptional activator could form an interplay with dual functional co-activator/histone acetyltransferases CBP/p300. This interplay resulted in substantial heterogeneity in H3K27ac, chromatin accessibility, and transcription. Simultaneous attenuation of CBP/p300 and HDAC4/5 reduced heterogeneity in the expression of endogenous genes, suggesting that this mechanism is universal. We further found that the noise was reduced by pulse-wide modulation of transcriptional activator binding possibly as a result of alternating the epigenetic states. Our findings suggest a mechanism for the modulation of noise in synthetic and endogenous gene expression systems.

A controllable gene expression system in liposomes that includes a positive feedback loop

2013 ◽  
Vol 9 (6) ◽  
pp. 1282 ◽  
Author(s):  
Shungo Kobori ◽  
Norikazu Ichihashi ◽  
Yasuaki Kazuta ◽  
Tetsuya Yomo
Keyword(s):  
Gene Expression ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Expression System ◽  
Positive Feedback Loop ◽  
Gene Expression System

scholarly journals A Histone Deacetylase 4/Myogenin Positive Feedback Loop Coordinates Denervation-dependent Gene Induction and Suppression

2009 ◽  
Vol 20 (4) ◽  
pp. 1120-1131 ◽  
Author(s):  
Huibin Tang ◽  
Peter Macpherson ◽  
Michael Marvin ◽  
Eric Meadows ◽  
William H. Klein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Deacetylase ◽  
Nicotinic Acetylcholine Receptor ◽  
Heavy Chain ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Gene Induction ◽  
Positive Feedback Loop ◽  
Nicotinic Acetylcholine ◽  
Histone Deacetylase 4

Muscle activity contributes to formation of the neuromuscular junction and affects muscle metabolism and contractile properties through regulated gene expression. However, the mechanisms coordinating these diverse activity-regulated processes remain poorly characterized. Recently, it was reported that histone deacetylase 4 (HDAC4) can mediate denervation-induced myogenin and nicotinic acetylcholine receptor gene expression. Here, we report that HDAC4 is not only necessary for denervation-dependent induction of genes involved in synaptogenesis (nicotinic acetylcholine receptor and muscle-specific receptor tyrosine kinase) but also for denervation-dependent suppression of genes involved in glycolysis (muscle-specific enolase and phosphofructokinase). In addition, HDAC4 differentially regulates genes involved in muscle fiber type specification by inducing myosin heavy chain IIA and suppressing myosin heavy chain IIB. Consistent with these regulated gene profiles, HDAC4 is enriched in fast oxidative fibers of innervated tibialis anterior muscle and HDAC4 knockdown enhances glycolysis in cultured myotubes. HDAC4 mediates gene induction indirectly by suppressing the expression of Dach2 and MITR that function as myogenin gene corepressors. In contrast, HDAC4 is directly recruited to myocyte enhancer factor 2 sites within target promoters to mediate gene suppression. Finally, we discovered an HDAC4/myogenin positive feedback loop that coordinates gene induction and repression underlying muscle phenotypic changes after muscle denervation.

Synthetic Gene Network with Positive Feedback Loop Amplifies Cellulase Gene Expression in Neurospora crassa

2018 ◽  
Vol 7 (5) ◽  
pp. 1395-1405 ◽  
Author(s):  
Toru Matsu-ura ◽  
Andrey A. Dovzhenok ◽  
Samuel T. Coradetti ◽  
Krithika R. Subramanian ◽  
Daniel R. Meyer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neurospora Crassa ◽  
Positive Feedback ◽  
Gene Network ◽  
Feedback Loop ◽  
Synthetic Gene ◽  
Cellulase Gene ◽  
Positive Feedback Loop ◽  
Synthetic Gene Network

scholarly journals FliZ Induces a Kinetic Switch in Flagellar Gene Expression

2010 ◽  
Vol 192 (24) ◽  
pp. 6477-6481 ◽  
Author(s):  
Supreet Saini ◽  
Santosh Koirala ◽  
Emily Floess ◽  
Patrick J. Mears ◽  
Yann R. Chemla ◽  
...  
Keyword(s):  
Gene Expression ◽  
Positive Feedback ◽  
Salmonella Enterica ◽  
Feedback Loop ◽  
Flagellar Gene ◽  
Positive Feedback Loop ◽  
Gene Expression Dynamics ◽  
Flagellar Assembly

ABSTRACT FliZ is an activator of class 2 flagellar gene expression in Salmonella enterica. To understand its role in flagellar assembly, we investigated how FliZ affects gene expression dynamics. We demonstrate that FliZ participates in a positive-feedback loop that induces a kinetic switch in class 2 gene expression.

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