How to tune an enhancer

Barolo, Scott

doi:10.1073/pnas.1606109113

Cited by 13 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In terms of sequence composition, the main focus is on the organization of TFBSs: their nature (activating, repressing, granting accessibility), their number, their orientation and spacing, their relative affinity for particular TFs, as well as the interactions of their cognate TFs (cooperative binding, synergy, competition, short-and long-range repression) (Barolo, 2016;Erceg et al, 2014;Long et al, 2016;Weingarten-Gabbay and Segal, 2014;Yanez-Cuna et al, 2013). TFBS organization has been under intense scrutiny in the last two decades (Evans et al, 2012;Hare et al, 2008;Khoueiry et al, 2010;Levo and Segal, 2014;Ludwig et al, 2000;Ludwig et al, 2011;Spitz and Furlong, 2012;Swanson et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Deciphering the regulatory logic of aDrosophilaenhancer through systematic sequence mutagenesis and quantitative image analysis

Poul

Xin

Ling

et al. 2020

Preprint

View full text Add to dashboard Cite

Transcriptional enhancers are short DNA sequences controlling the spatial activity, timing and levels of eukaryotic gene transcription. Their quantitative transcriptional output is thought to result from the number and organization of transcription factor binding sites (TFBSs). Yet, how the various aspects of regulatory information are encoded in enhancer sequences remains elusive. We addressed this question by quantifying the spatial activity of the yellow spot enhancer active in developing Drosophila wings. To identify which enhancer DNA sequence contributes to enhancer activity, we introduced systematic mutations along the enhancer. We developed an analytic framework that uses comprehensive descriptors to quantify reporter assay in transgenic Deciphering the regulatory logic of an enhancer 2 flies and measure spatial variations in activity levels across the wing. Our analysis highlights an unexpected density of regulatory information in the spot enhancer sequence. Furthermore, it reveals an unanticipated regulatory logic underlying the activity of this enhancer, and how it reads the wing trans-regulatory landscape to encode a spatial pattern.Deciphering the regulatory logic of an enhancer

show abstract

Section: Introductionmentioning

confidence: 99%

Deciphering the regulatory logic of aDrosophilaenhancer through systematic sequence mutagenesis and quantitative image analysis

Poul

Xin

Ling

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…[46]), by changing their original promoters for others with different initiation kinetics (strength and, in particular, relative duration of the rate-limiting steps in transcription initiation [13,18,23]). Similar tests could be performed by changing the binding affinities of TFs to the promoters, whose original values can be found in [15,92–94], as these changes are expected to also allow changes in the transcription initiation kinetics of the genes composing the circuits.…”

Section: Discussionmentioning

confidence: 99%

Added value of autoregulation and multi-step kinetics of transcription initiation

Prajapat

Ribeiro

2018

R. Soc. open sci.

View full text Add to dashboard Cite

Bacterial gene expression regulation occurs mostly during transcription, which has two main rate-limiting steps: the close complex formation, when the RNA polymerase binds to an active promoter, and the subsequent open complex formation, after which it follows elongation. Tuning these steps' kinetics by the action of e.g. transcription factors, allows for a wide diversity of dynamics. For example, adding autoregulation generates single-gene circuits able to perform more complex tasks. Using stochastic models of transcription kinetics with empirically validated parameter values, we investigate how autoregulation and the multi-step transcription initiation kinetics of single-gene autoregulated circuits can be combined to fine-tune steady state mean and cell-to-cell variability in protein expression levels, as well as response times. Next, we investigate how they can be jointly tuned to control complex behaviours, namely, time counting, switching dynamics and memory storage. Overall, our finding suggests that, in bacteria, jointly regulating a single-gene circuit's topology and the transcription initiation multi-step dynamics allows enhancing complex task performance.

show abstract

“…Today, new technologies offer new treatment options. There are now a variety of methods for blocking protein interactions with DNA or RNA (e.g., CRISPR-CAS9 technologies, anti-sense oligonucleotides, DNA decoys or small inhibitory molecules [ 113 , 116 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 ]). Perhaps fine-tuned and targeted manipulations of nuclear receptor binding sites within promoters, enhancers and switch sites of the immunoglobulin loci will ultimately prove successful for the control and optimization of immunoglobulin expression.…”

Section: When B Cells Need Correctionmentioning

confidence: 99%

Nuclear Receptors, Ligands and the Mammalian B Cell

Jones

Penkert

Surman

et al. 2020

IJMS

View full text Add to dashboard Cite

Questions concerning the influences of nuclear receptors and their ligands on mammalian B cells are vast in number. Here, we briefly review the effects of nuclear receptor ligands, including estrogen and vitamins, on immunoglobulin production and protection from infectious diseases. We describe nuclear receptor interactions with the B cell genome and the potential mechanisms of gene regulation. Attention to the nuclear receptor/ligand regulation of B cell function may help optimize B cell responses, improve pathogen clearance, and prevent damaging responses toward inert- and self-antigens.

show abstract

How to tune an enhancer

Cited by 13 publications

References 20 publications

Deciphering the regulatory logic of aDrosophilaenhancer through systematic sequence mutagenesis and quantitative image analysis

Deciphering the regulatory logic of aDrosophilaenhancer through systematic sequence mutagenesis and quantitative image analysis

Added value of autoregulation and multi-step kinetics of transcription initiation

Nuclear Receptors, Ligands and the Mammalian B Cell

Contact Info

Product

Resources

About