Limits...
Structure of silent transcription intervals and noise characteristics of mammalian genes.

Zoller B, Nicolas D, Molina N, Naef F - Mol. Syst. Biol. (2015)

Bottom Line: Strikingly, endogenous or synthetic promoters with TATA boxes show simplified two-state promoter cycles.Since transcriptional bursting constrains intrinsic noise depending on the number of promoter steps, this explains why TATA box genes display increased intrinsic noise genome-wide in mammals, as revealed by single-cell RNA-seq.These findings have implications for basic transcription biology and shed light on interpreting single-cell RNA-counting experiments.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

No MeSH data available.


Related in: MedlinePlus

Structure and kinetics of the promoter cycles for the NIH3T3 clonesBurst size vs. the fraction of time the gene is active. Each clone is represented by a 95% confidence ellipse from the posterior distribution. All the analyzed clones burst, characterized by small activity fractions. Burst sizes show a large dynamic range across clones (˜80-fold). Inset: Magnification of the lower left corner.Burst size vs. the total silent period T. Elongated confidence ellipses reflect the dependence between those two quantities and the mean mRNA. Although the dynamic range of the silent period (˜6-fold) is smaller than for the burst size, it is also gene specific. The synthetic (warm colors) and endogenous (cold colors) promoters cluster in distinct regions.Number of inactive states vs. T, crosses indicate mean and error bars stand for the 5th and 95th percentiles of the posterior. Endogenous promoters tend to show more inactive steps and shorter cycle times (cluster around N˜6 and T˜60 min) compared to synthetic promoters (cluster around N˜1–2 and T˜130 min).Partitioning of the silent period for the optimal models. The light and dark bars show the mean durations of each sub-step. Partitions in endogenous promoters tend to be more uniform compared to the synthetic promoters. Average inactive times for endogenous promoter are around 10 min, whereas synthetic promoters have average inactive times close to 100 min (˜115 min for the first and ˜25 min for the subsequent intervals).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4547851&req=5

fig03: Structure and kinetics of the promoter cycles for the NIH3T3 clonesBurst size vs. the fraction of time the gene is active. Each clone is represented by a 95% confidence ellipse from the posterior distribution. All the analyzed clones burst, characterized by small activity fractions. Burst sizes show a large dynamic range across clones (˜80-fold). Inset: Magnification of the lower left corner.Burst size vs. the total silent period T. Elongated confidence ellipses reflect the dependence between those two quantities and the mean mRNA. Although the dynamic range of the silent period (˜6-fold) is smaller than for the burst size, it is also gene specific. The synthetic (warm colors) and endogenous (cold colors) promoters cluster in distinct regions.Number of inactive states vs. T, crosses indicate mean and error bars stand for the 5th and 95th percentiles of the posterior. Endogenous promoters tend to show more inactive steps and shorter cycle times (cluster around N˜6 and T˜60 min) compared to synthetic promoters (cluster around N˜1–2 and T˜130 min).Partitioning of the silent period for the optimal models. The light and dark bars show the mean durations of each sub-step. Partitions in endogenous promoters tend to be more uniform compared to the synthetic promoters. Average inactive times for endogenous promoter are around 10 min, whereas synthetic promoters have average inactive times close to 100 min (˜115 min for the first and ˜25 min for the subsequent intervals).

Mentions: The clones spanned a wide range of burst sizes b (from 1 to 80), independent of the fraction of time spent in the active state, which remained under 10% (Fig3A). The infrequent promoter activations clearly indicated that transcription occurs in bursts. Moreover, b depended predominantly on the promoter and, to a lesser extent, on the genomic locus, as exemplified by multiple Bmal1 and H1 clones. The average duration of the silent period T exhibited a smaller dynamic range (from 30 min to 3 h) than the burst sizes, which was the most varying kinetic parameter among the clones (Fig3B). Notably, b and T appeared largely uncorrelated among the clones. Overall, the extended model yielded kinetic parameters that were largely consistent with previous estimates (Suter et al, 2011) (Table EV3). Clearly, the short activation times and large burst sizes implied that transcription in this set of clones is highly discontinuous.


Structure of silent transcription intervals and noise characteristics of mammalian genes.

Zoller B, Nicolas D, Molina N, Naef F - Mol. Syst. Biol. (2015)

Structure and kinetics of the promoter cycles for the NIH3T3 clonesBurst size vs. the fraction of time the gene is active. Each clone is represented by a 95% confidence ellipse from the posterior distribution. All the analyzed clones burst, characterized by small activity fractions. Burst sizes show a large dynamic range across clones (˜80-fold). Inset: Magnification of the lower left corner.Burst size vs. the total silent period T. Elongated confidence ellipses reflect the dependence between those two quantities and the mean mRNA. Although the dynamic range of the silent period (˜6-fold) is smaller than for the burst size, it is also gene specific. The synthetic (warm colors) and endogenous (cold colors) promoters cluster in distinct regions.Number of inactive states vs. T, crosses indicate mean and error bars stand for the 5th and 95th percentiles of the posterior. Endogenous promoters tend to show more inactive steps and shorter cycle times (cluster around N˜6 and T˜60 min) compared to synthetic promoters (cluster around N˜1–2 and T˜130 min).Partitioning of the silent period for the optimal models. The light and dark bars show the mean durations of each sub-step. Partitions in endogenous promoters tend to be more uniform compared to the synthetic promoters. Average inactive times for endogenous promoter are around 10 min, whereas synthetic promoters have average inactive times close to 100 min (˜115 min for the first and ˜25 min for the subsequent intervals).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4547851&req=5

fig03: Structure and kinetics of the promoter cycles for the NIH3T3 clonesBurst size vs. the fraction of time the gene is active. Each clone is represented by a 95% confidence ellipse from the posterior distribution. All the analyzed clones burst, characterized by small activity fractions. Burst sizes show a large dynamic range across clones (˜80-fold). Inset: Magnification of the lower left corner.Burst size vs. the total silent period T. Elongated confidence ellipses reflect the dependence between those two quantities and the mean mRNA. Although the dynamic range of the silent period (˜6-fold) is smaller than for the burst size, it is also gene specific. The synthetic (warm colors) and endogenous (cold colors) promoters cluster in distinct regions.Number of inactive states vs. T, crosses indicate mean and error bars stand for the 5th and 95th percentiles of the posterior. Endogenous promoters tend to show more inactive steps and shorter cycle times (cluster around N˜6 and T˜60 min) compared to synthetic promoters (cluster around N˜1–2 and T˜130 min).Partitioning of the silent period for the optimal models. The light and dark bars show the mean durations of each sub-step. Partitions in endogenous promoters tend to be more uniform compared to the synthetic promoters. Average inactive times for endogenous promoter are around 10 min, whereas synthetic promoters have average inactive times close to 100 min (˜115 min for the first and ˜25 min for the subsequent intervals).
Mentions: The clones spanned a wide range of burst sizes b (from 1 to 80), independent of the fraction of time spent in the active state, which remained under 10% (Fig3A). The infrequent promoter activations clearly indicated that transcription occurs in bursts. Moreover, b depended predominantly on the promoter and, to a lesser extent, on the genomic locus, as exemplified by multiple Bmal1 and H1 clones. The average duration of the silent period T exhibited a smaller dynamic range (from 30 min to 3 h) than the burst sizes, which was the most varying kinetic parameter among the clones (Fig3B). Notably, b and T appeared largely uncorrelated among the clones. Overall, the extended model yielded kinetic parameters that were largely consistent with previous estimates (Suter et al, 2011) (Table EV3). Clearly, the short activation times and large burst sizes implied that transcription in this set of clones is highly discontinuous.

Bottom Line: Strikingly, endogenous or synthetic promoters with TATA boxes show simplified two-state promoter cycles.Since transcriptional bursting constrains intrinsic noise depending on the number of promoter steps, this explains why TATA box genes display increased intrinsic noise genome-wide in mammals, as revealed by single-cell RNA-seq.These findings have implications for basic transcription biology and shed light on interpreting single-cell RNA-counting experiments.

View Article: PubMed Central - PubMed

Affiliation: The Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

No MeSH data available.


Related in: MedlinePlus